Dear colleague,
Please find below seven Press Releases relating to late breaking trials being presented at ESMO 2016 today.
-
Significant survival gains with atezolizumab vs docetaxel for non-small-cell lung cancer
-
Nivolumab maintains function and reduces symptoms in relapsed metastatic head and neck cancer
-
Pembrolizumab new option for first line treatment of patients with advanced lung cancer and high PD-L1 expression
-
First-line pembrolizumab plus chemotherapy significantly improves outcomes in advanced NSCLC
-
Ceritinib provides longer progression-free survival than chemotherapy in phase III trial of ALK rearranged lung cancer treatment
-
Greater patient selection may be needed for first line nivolumab to improve progression-free survival in advanced lung cancer
-
Nintedanib improves progression-free survival but not overall survival in phase III trial of metastatic colorectal cancer
Kind regards
ESMO Press Office
PRESS RELEASE
EMBARGOED until 9 October 2016, 8:15 hours (CEST)
Significant survival gains with atezolizumab vs docetaxel for non-small-cell lung cancer
LUGANO-COPENHAGEN, 9 October, 2016 – The first phase III study of PD-L1 inhibitor atezolizumab in previously-treated non-small-cell lung cancer has seen significant improvements in survival compared to standard chemotherapy, researchers reported today at the ESMO 2016 Congress in Copenhagen1.
PD-L1 inhibitors are of a class of cancer immunotherapies called checkpoint inhibitors, and work by inhibiting one of the mechanisms of resistance developed by cancer cells in order to evade the immune system.
“The goal of this treatment is to allow the immune system to control and possibly eliminate cancer calls, so atezolizumab might be useful in a very large setting of different cancers,” said investigator Dr. Fabrice Barlesi, head of Multidisciplinary Oncology and Therapeutic Innovations Deparment at Aix-Marseille University and the Assistance Publique Hôpitaux de Marseille, France.
The OAK study enrolled 1225 patients with previously treated non-small-cell lung cancer and, after stratifying them according to PD-L1 status, number of prior chemotherapy regimens and histology, randomised them to intravenous atezolizumab (1200mg every 3 weeks) or docetaxel (75 mg/m2 every 3 weeks).
In the preliminary analysis of data from 850 patients, researchers saw a 27% improvement in overall survival in the patients receiving azetolizumab compared to those treated with docetaxel (p=0.0003), regardless of their PD-L1 expression levels and including patients with PD-L1 expression of less than 1%.
When patients were stratified according to their level of PD-L1 expression, the overall survival was 59% greater among patients in the highest tertile of PD-L1 expression who were treated with azetolizumab, compared to the same group treated with docetaxel (P < 0.0001).
However even in patients with no PD-L1 expression, there was still a significant 25% improvement in overall survival with atezolizumab compared to those treated with docetaxel. The improvements in overall survival were similar in patients with squamous and non-squamous histology.
“This is the first phase III study of atezolizumab, a PD-L1 inhibitor, and it confirms the efficacy seen in the POPLAR phase II study, along with the results of PD-1 inhibitors” said Barlesi.
“Azetizolumab offers a new second-line therapeutic strategy for patients with non-small-cell lung cancer, regardless of the PD-L1 status of the tumor.”
Commenting on the study, Professor Martin Reck, from the Department of Thoracic Oncology at
Lung Clinic Grosshansdorf, Germany, said: “This is a very important piece of information on the role of PD-L1/PD-1 antibodies in treatment of non-small-cell lung cancer, and confirms the overall survival benefits shown in the POPLAR and CHECKMATE trials.”
“Interestingly, the study also showed an improvement in overall survival, even in patients with no PD-L1 expression, which means we have a problem with using PD-L1 negativity as an exclusion factor for treatment,” Reck explained.
“My suggestion would be that PD-L1 is perhaps one imperfect surrogate marker to describe the activity; it’s a good enrichment factor but we need additional markers for the characterization of patients who might not benefit from this treatment or who might really benefit.”
-END-
Notes to Editors
References
1 Abstract LBA44_PR – “Primary analysis from OAK, a randomized phase III study comparing atezolizumab with
docetaxel in 2L/3L NSCLC” will be presented by Dr Fabrice Barlesi during the Presidential Symposium 2 on Sunday 9 October, 16:25 to 18:20 (CEST)
Disclaimer
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .
About the European Society for Medical Oncology
ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.
Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.
Abstract for LBA44_PR
Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC
F. Barlesi1, K. Park2, F. Ciardiello3, J. von Pawel4, S. Gadgeel5, T. Hida6, D. Kowalski7, M.C. Dols8, D. Cortinovis9, J. Leach10, J. Polikoff11, D. Gandara12, C.H. Barrios13, D.S. Chen14, P. He15, M. Kowanetz16, M. Ballinger17, D. Waterkamp14, A. Sandler14, A. Rittmeyer18
1Assistance Publique Hôpitaux de Marseille, Aix Marseille University, Marseille, France, 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 3Medical Oncology, AOU Seconda Università degli Studi di Napoli (AOU-SUN), Naples, Italy, 4Oncology, Asklepios-Fachklinikum, Gauting, Germany, 5Wayne State University, Karmanos Cancer Institute, Detroit, MI, USA, 6Aichi Cancer Center Hospital, Nagoya, Japan, Aichi Cancer Center Hospital, Nagoya, Japan, Nagoya, Japan, 7Department of Lung Cancer and Chest Tumours, The Maria Sklodowska-Curie Institute of Oncology, Warsaw, Poland, 8Medical Oncology Section, Hospital Universitario Málaga General Carlos Haya, Malaga, Spain, 9Dept. of Medical Oncology, Azienda Ospedaliera San Gerardo Hospital, Monza, Italy, 10Medical Oncology, Metro-Minnesota Community Oncology Research Consortium, Minneapolis, MN, USA, 11Oncology, Southern California Permanente Medical Group, San Diego, CA, USA, 12Internal Medicine, University of California Davis Cancer Center, Sacramento, CA, USA, 13Department of Medicine, Pontifical Catholic University of Rio Grande do Sul School of Medicine, Porto Alegre, Brazil, 14Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA, 15Biostatistics, Genentech, Inc., South San Francisco, USA, 16Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA, 17Product Development, Oncology, Genentech, Inc., South San Francisco, CA, USA, 18Oncology, Lungenfachklinik Immenhausen, Immenhausen, Germany
Background: Atezolizumab (atezo) inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity, while leaving the PD-L2/PD-1 interaction intact. Atezo demonstrated survival benefit vs docetaxel (doc) in the Ph2 trial POPLAR. Here we present the primary analysis from the Ph3 OAK study evaluating atezo vs doc in previously treated NSCLC.
Methods: Previously treated NSCLC patients (pts) were stratified by PD-L1 status, prior chemotherapy regimens (1 vs 2) and histology, and randomized 1:1 to atezo (1200 mg IV q3w) or doc (75 mg/m2 IV q3w). The co-primary endpoints were OS in the ITT and PD-L1–expression subgroup TC1/2/3 or IC1/2/3 (PD-L1 expression on ≥ 1% TC or IC). Secondary endpoints included PFS, ORR, DoR and safety.
Results: The primary efficacy analysis was conducted in the first 850 of 1225 total enrolled pts. Pts had a median age of 64 y, 61% were male, 25% had 2 prior lines of therapies, 26% had squamous histology, 67% were previous smokers and 37% were PS 0. Superior OS was seen with atezo vs doc in ITT (HR 0.73; P = .0003) and TC1/2/3 or IC1/2/3 pts (HR 0.74; P = .0102). Survival was improved regardless of PD-L1 expression levels, including in pts with no PD-L1 expression (TC0 and IC0). There was pronounced benefit in pts with high PD-L1 expression (TC3 or IC3). OS benefit was similar in pts with squamous or nonsquamous histology. In ITT pts, PFS HR was 0.95 (2.8 vs 4.0 mo), ORR 13.6% vs 13.4%, and DoR 16.3 vs 6.2 mo for atezo vs doc. Gr 3-4 treatment-related AEs occurred in 15% of atezo pts and 43% of doc pts. There were no deaths related to atezo and 1 related to doc. No new safety signal was observed.
Conclusions: This first Ph3 trial of a PD-L1-directed drug in NSCLC demonstrates that atezo treatment results in a statistically significant and clinically relevant improvement in OS vs doc in 2L/3L NSCLC, regardless of PD-L1 expression and histology. Atezo was well tolerated with a favorable safety profile vs doc.
|
|
OS |
|||||
|
|
Atezo |
Doc |
HRa |
P Value |
||
|
|
n |
Median, mo |
n |
Median, mo |
||
|
ITT |
425 |
13.8 |
425 |
9.6 |
0.73 |
0.0003b |
|
TC1/2/3 or IC1/2/3 |
241 |
15.7 |
222 |
10.3 |
0.74 |
0.0102b |
|
TC2/3 or IC2/3 |
129 |
16.3 |
136 |
10.8 |
0.67 |
0.0080 |
|
TC3 or IC3 |
72 |
20.5 |
65 |
8.9 |
0.41 |
<0.0001 |
|
TC0 and IC0 |
180 |
12.6 |
199 |
8.9 |
0.75 |
0.0215 |
|
Squamous |
112 |
8.9 |
110 |
7.7 |
0.73 |
0.0383 |
|
Nonsquamous |
313 |
15.6 |
315 |
11.2 |
0.73 (0.60, 0.89) |
0.0015 |
|
TC, tumor cell; IC, tumor infiltrating immune cells. PD-L1 expression was centrally evaluated with the VENTANA SP142 IHC assay |
||||||
Clinical trial identification: NCT02008227
Legal entity responsible for the study: F. Hoffmann-La Roche Ltd
Funding: F. Hoffmann-La Roche Ltd
|
Disclosure: |
K. Park: Consultant: Astellas, Astra-Zeneca, Aveo, Boehringer Ingelheim, Clovis, Eli Lilly, Hanmi, KHK Novartis, Ono, Roche Research funding: Astra-Zeneca. |
Keywords: atezolizumab, NSCLC, cancer immunotherapy
PRESS RELEASE
EMBARGOED until 9 October 2016, 08:15 hours (CEST)
Nivolumab maintains function and reduces symptoms in relapsed metastatic head and neck cancer
LUGANO-COPENHAGEN, 9 October, 2016 – Nivolumab maintains function and reduces symptoms in treatment of relapsed metastatic head and neck cancer, according to results from the CheckMate 141 trial presented at the ESMO 2016 Congress in Copenhagen1 and published in the New England Journal of Medicine.2
CheckMate 141 is a randomised, open label phase III trial in which 361 patients with platinum refractory relapsed head and neck cancer received treatment with nivolumab or standard of care chemotherapy (physician’s choice of methotrexate, docetaxel or cetuximab). As previously reported, nivolumab improved overall survival by an average of 2.5 months.
For the first time today the investigators presented the results of patient reported outcomes, including functional capacity and symptoms. The analysis included 129 patients who completed questionnaires3 at baseline, nine weeks and at six week intervals during treatment. Questions covered functional areas, such as their physical ability to perform their role in life (job, etc) and their emotional, cognitive and social wellbeing. They were also asked about symptoms such as fatigue, nausea, pain and shortness of breath. An overall score was calculated for global health.
Within each treatment arm the questionnaire results were tracked from baseline to nine weeks and 15 weeks. The investigators also compared the results between the two treatment arms at nine weeks and 15 weeks using previously defined score differences defining a clinically relevant gap (for some domains it was a gap of seven points while for others it was a gap of ten points).
For patients receiving nivolumab, both function and symptom burden was maintained or even improved at nine and 15 weeks compared to baseline. In contrast, patients receiving standard of care chemotherapy had worse scores in all areas at nine and 15 weeks compared to baseline.
When the investigators compared the scores between the two treatment arms at nine and 15 weeks, they found that for most of the function and symptom areas, nivolumab gave a clinical significant benefit over standard of care chemotherapy.
“Nivolumab not only prolongs life but it does so while maintaining function and reducing symptoms compared with standard of care chemotherapy,” said lead author Professor Kevin Harrington, joint head of the Division of Radiotherapy and Imaging, at the Institute of Cancer Research, London, UK and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust.
“We need to drill down into the data to understand the reasons for these findings,” he continued. “The data suggest that the superior clinical activity of nivolumab maintains patient-reported outcomes, but it is also likely that nivolumab is a kinder treatment that is associated with fewer side effects which can have a negative effect on quality of life.”
“We’re used to the notion that for gain there has to be pain, and that we have to ask patients to accept more toxicity to get better outcomes,” said Harrington. “But immunotherapy with nivolumab gives better survival and allows patients to function at work and socially, and experience less pain and fatigue than with chemotherapy. This is a win-win scenario for patients and their doctors.”
Commenting on the study, Professor Sandrine Faivre, a medical oncologist at Beaujon University Hospital, Clichy, France said: “This study assessed symptoms and quality of life using several questionnaires, including one specifically designed for patients with head and neck cancer. This is important because these tumours have particular consequences. A tumour mass in the neck, for example, is painful and may impair eating and speaking functions. It is also visible and can lead to social isolation.”
“This is the first study to show that an immunotherapy is superior to classical treatment options for improving quality of life and symptoms, on top of prolonging survival,” continued Faivre. “I can now explain to my patients that nivolumab may help them to feel and function better in daily life.”
She concluded: “Nivolumab works in around one-third of patients with advanced head and neck cancer. We need biomarkers or biological criteria to identify patients most likely to benefit from this treatment so that unnecessary side effects and costs are avoided.”
-END-
Notes to Editors
References and notes
1 Abstract LBA4 - ‘Patient-Reported Outcomes (PROs) in Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck (SCCHN) Treated with Nivolumab (Nivo) or Investigator’s Choice (IC): CheckMate 141,‘ will be presented by Professor Kevin Harrington during Presidential Symposium 2 on Sunday, 9 October, 16:30 – 18:20 (CEST).
2 Gillison M, Ferris R, Blumenschein G, et al. Nivolumab for recurrent squamous cell carcinoma of the head and neck. N Engl J Med. DOI: 10.1056/NEJMoa1602252
3 The questionnaires were the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), EORTC Head and Neck Cancer module (QLQ-H&N35) and the EuroQol five dimensions’ questionnaire (EQ-5D).
Disclaimer
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .
About the European Society for Medical Oncology
ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.
Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.
ABSTRACT LBA4_PR
Patient-Reported Outcomes (PROs) in Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck (SCCHN) Treated with Nivolumab (Nivo) or Investigator’s Choice (IC): CheckMate 141
K. Harrington1, R.L. Ferris2, J. Shaw3, F. Taylor4, M. Derosa4, D. Turner-Bowker4, L. Morrissey4, K. Cocks5, N. Kiyota6, M. Gillison7, J. Guigay8
1Division of Radiotherapy and Imaging, Institute of Cancer Research ICR, London, UK, 2Division of Head and Neck Surgery Departments of Otolaryngology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA, 3Clinical Outcomes Assessment and I-O LCM Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA, 4Patient-Centered Outcomes, Adelphi Values, Boston, MA, USA, 5Patient-Centered Outcomes, Adelphi Values, Cheshire, UK, 6Medicine of Oncology, Kobe University Hospital, Kobe, Japan, 7Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA, 8Medical Oncology Department, Centre Antoine Lacassagne, Nice, France
Background: Patients (pts) with platinum-refractory R/M SCCHN have median survival ≤6 mo and suffer from their disease and its treatment. Accordingly, maintaining quality of life (QoL) is a key treatment goal. PRO data were collected as exploratory endpoints in CheckMate 141 (NCT02105636), a randomized, open-label, phase 3 trial comparing nivo to IC (methotrexate, docetaxel, or cetuximab) in 361 pts with platinum-refractory R/M SCCHN. We report the first comparative results for PRO for nivo and IC in R/M SCCHN.
Methods: The European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ-C30), EORTC Head and Neck Cancer module (QLQ-H&N35), and EQ-5D were administered at baseline (BL), wk 9, and then at 6-wk intervals during treatment. A clinically relevant score change or difference was regarded as 10 points for the EORTC subscales. Analysis of covariance (ANCOVA) was applied to compare mean score changes between arms. Proportional hazards regression was used to evaluate time to clinically relevant score deterioration (TTD).
Results: BL questionnaire completion rates for nivo and IC were ~80% and ~75%, respectively. Low IC completion rates precluded analysis of mean differences after wk 15. Overall, 129 pts completed a PRO measure at BL and during follow up. Nivo significantly delayed TTD (P<0.05, 2-tailed) vs IC for global health; physical, role, cognitive, and social functioning; fatigue; dyspnea; and insomnia (EORTC QLQ-C30) as well as pain; sensory problems; and mouth opening problems (QLQ-H&N35). ANCOVA revealed statistically significant, clinically relevant differences favoring nivo at wks 9 and 15 for role and social functioning, fatigue, dyspnea, and appetite loss (EORTC QLQ-C30) as well as pain and sensory problems (QLQ-H&N35). Differences in mean values were observed for other PROs at wk 15 only.
Conclusions: Pts treated with nivo had delayed worsening of functioning and symptoms with PRO differences between arms favoring nivo up to ~4 mo of follow up. These results, as assessed through wk 15, suggest that pts receiving nivo maintained functioning for longer and had less pain, fatigue, and dyspnea on treatment as compared with IC.
Clinical trial identification: NCT02105636; Study start date, May 2014
Legal entity responsible for the study: Sponsored by Bristol-Myers Squibb
Funding: Bristol-Myers Squibb
|
Disclosure: |
K. Harrington: Personal fees and fees paid to research institution from BMS, during the study; Fees paid to research institution by AstraZeneca and Pfizer; Personal fees and fees paid to research institution from Merck and Amgen, outside submitted work. |
Keywords: patient reported outcomes, quality of life, head and neck cancer
PRESS RELEASE
EMBARGOED until 9 October 2016, 8:15 hours (CEST)
Pembrolizumab new option for first line treatment of patients with advanced lung cancer and high PD-L1 expression
LUGANO-COPENHAGEN, 9 October, 2016 – Pembrolizumab is set to become a new option for first line treatment of patients with advanced lung cancer and high PD-L1 expression, according to the results of the phase III KEYNOTE-024 trial presented at the ESMO 2016 Congress in Copenhagen1 and published in the New England Journal of Medicine.2
”Pembrolizumab is a PD-1 antibody approved for second line treatment of patients with advanced non-small-cell lung cancer (NSCLC) and PD-L1 expression in their tumour cells,” said lead author Professor Martin Reck, chief oncology physician, Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. “KEYNOTE-024 is the first phase III trial of pembrolizumab as first line treatment in patients with high PD-L1 expression, who represent 27–30% of those with advanced NSCLC.”
KEYNOTE-024 investigated the efficacy of pembrolizumab compared to standard of care with platinum-based chemotherapy in untreated patients with advanced NSCLC and high PD-L1 expression (defined as expression in at least 50% of tumour cells). Patients with EGFR activating mutations and ALK translocations were excluded from recruitment. “There is a substantial need to find better options than chemotherapy for these patients,” said Reck.
The trial included 305 patients from 16 countries who were randomised 1:1 to pembrolizumab or chemotherapy. Patients in the chemotherapy arm who progressed were eligible to crossover to pembrolizumab as second line treatment – this occurred in 44% of these patients.
The investigators found that pembrolizumab significantly improved the primary endpoint of progression-free survival by approximately four months compared to chemotherapy (10.3 months versus 6.0 months, hazard ratio [HR] 0.50). The secondary endpoint of overall survival was also significantly prolonged, and 80% of patients on pembrolizumab were alive at six months compared to 72% on chemotherapy (HR=0.60).
“The significant improvement in overall survival with pembrolizumab was remarkable given that more than 40% of patients crossed over from the control arm to pembrolizumab after progression of the disease,” said Reck.
Pembrolizumab was associated with a higher overall response rate compared to chemotherapy (45% versus 28%), a longer duration of response, and lower incidences of all and serious (3/4) adverse events.
“This data will completely change the management of patients with advanced NSCLC,” said Reck. “All endpoints of efficacy and tolerability favoured treatment with pembrolizumab, suggesting it should become one standard of care for first line treatment of patients with advanced NSCLC and high PD-L1 expression. This is primarily an opportunity for patients without oncogenic alterations. More information is needed for those with alterations.”
He concluded: “This is a landmark trial for the 30% of patients with advanced NSCLC who are high expressers of PD-L1. The new treatment algorithm should include upfront testing for PD-L1 expression to identify patients who will benefit from first line treatment with pembrolizumab.”
Commenting on the results, Professor Johan Vansteenkiste, Professor of Medicine, Catholic University Leuven, and Chief Oncology Physician, Unit of Respiratory Oncology, University Hospital KU Leuven, Belgium, said: “This study may change current practice for the treatment of patients with advanced NSCLC. It is the first time a therapy has improved progression-free survival over the current standard first line treatment with platinum-based doublet chemotherapy.”
“The reason KEYNOTE-024 met its primary endpoint, in contrast with other studies, is probably because the trial only included patients who had PD-L1 expression of at least 50% and were therefore optimal candidates for treatment with pembrolizumab,” he added.
“A study is needed to confirm these findings in patients with high PD-L1 expression,” continued Vansteenkiste. “Additional research should be done to find out whether patients with lower levels of PD-L1 expression also benefit more from pembrolizumab than chemotherapy.”
-END-
Notes to Editors
References
1 Abstract LBA8_PR ‘KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) >50%‘ will be presented by Professor Martin Reck during the Presidential Symposium 2 on Sunday, 9 October 2016, 16:25 to 18:20 (CEST) in Room Copenhagen.
2 Reck M, Rodríguez-Abreu D, Robinson A, et al. Pembrolizumab or Chemotherapy in PD-L1–Positive Non–Small-Cell Lung Cancer. N Engl J Med. DOI: 10.1056/NEJMoa1606774
Disclaimer
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .
About the European Society for Medical Oncology
ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.
Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.
Abstract for LBA8_PR
KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%
M. Reck1, D. Rodríguez-Abreu2, A.G. Robinson3, R. Hui4, T. Csoszi5, A. Fülöp6, M. Gottfried7, N. Peled8, A. Tafreshi9, S. Cuffe10, M. O'Brien11, S. Rao12, K. Hotta13, M. Leiby14, G.M. Lubiniecki15, Y. Shentu16, R. Rangwala15, J.R. Brahmer17
1Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Grosshansdorf, Germany, 2Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas De Gran Canaria, Spain, 3Oncology, Cancer Centre of Southeastern Ontario at Kingston General Hospital and Queens University, Kingston, ON, Canada, 4Medical Oncology, Westmead Hospital and University of Sydney, Sydney, Australia, 5Onkologiai Kozpont, Hetenyi G Korhaz, Szolnok, Hungary, 6Oncology, National Koranyi Institute of Pulmonology, Budapest, Hungary, 7Oncology, Meir Medical Center, Kfar Saba, Israel, 8Thoracic Cancer Unit, Davidoff Cancer Center, Petach Tiqwa, Israel, 9Medical Oncology, Southern Medical Day Care Centre, Wollongong, Australia, 10Medical Oncology, St James's Hospital, Dublin, Ireland, 11Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, London, UK, 12Oncology, MedStar Franklin Square Medical Center, Baltimore, MD, USA, 13Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan, 14Global Scientific and Medical Publications, Merck & Co., Inc., Kenilworth, NJ, USA, 15Oncology Clinical Development, Merck & Co., Inc., Kenilworth, NJ, USA, 16Biostatistics and Research Decision Statistics, Merck & Co., Inc., Kenilworth, NJ, USA, 17Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
Background: Platinum-based doublet chemo is the standard first-line therapy for advanced NSCLC without a treatable oncogenic aberration. Pembro (anti–PD-1) is approved in the US and EU for previously treated, PD-L1–expressing advanced NSCLC. KEYNOTE-024 (NCT02142738) is an open-label, phase 3 study of pembro vs platinum-doublet chemo as first-line therapy for advanced NSCLC of PD-L1 TPS ≥50% without treatable EGFR mutations or ALK translocations.
Methods: Patients (pts) were randomized to 35 cycles of pembro 200 mg Q3W or 4-6 cycles of investigator’s choice of carboplatin or cisplatin + pemetrexed, carboplatin or cisplatin + gemcitabine, or carboplatin + paclitaxel, with optional pemetrexed maintenance for nonsquamous NSCLC. Pts in the chemo arm could crossover to pembro upon PD. Response was assessed every 9 wk (RECIST v1.1, central imaging vendor). Primary end point was PFS. Secondary end points were OS, ORR, and safety. Differences in PFS and OS were assessed in the ITT population using the stratified log-rank test. At the prespecified second interim analysis (data cutoff, May 9, 2016), the study had 97% power to detect a HR of 0.55 for PFS at a 1-sided α = 2.0%.
Results: From Sep 19, 2014, to Oct 29, 2015, 305 pts from 16 countries were randomized: 154 to pembro, 151 to chemo. After a median follow-up of 11.2 mo, 48% of pts remained on pembro, 10% remained on chemo, and 44% crossed over from chemo to pembro upon PD. With 189 events, pembro significantly prolonged PFS over chemo (HR 0.50, 95% CI 0.37-0.68, P < 0.001; median 10.3 mo vs 6.0 mo). With 108 deaths, pembro also significantly prolonged OS (HR 0.60, 95% CI 0.41-0.89, P = 0.005; 6-mo OS 80% vs 72%). Pembro was also associated with higher ORR (45% vs 28%), longer response duration (median NR vs 6.3 mo), and lower incidence of any-grade (73% vs 90%) and grade 3-5 (27% vs 53%) treatment-related AEs.
Conclusions: Pembro demonstrated superior PFS and OS over platinum-based chemo in pts with advanced NSCLC of PD-L1 TPS ≥50%. Along with the lower rate of treatment-related AEs, these data suggest pembro may be the new standard of care for first-line therapy of PD-L1–expressing advanced NSCLC without treatable oncogenic aberrations.
Clinical trial identification: ClinicalTrials.gov number NCT02142738, originally posted May 16, 2014; EudraCT number 2014-000323-25, originally issued 27-Mar-2014
Legal entity responsible for the study: Merck & Co., Inc.
Funding: Merck & Co., Inc.
|
Disclosure: |
M. Reck: Served as Advisory board member for Roche, Lilly, BMS, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. Also, served on Speakers’ bureau for Roche, Lilly, BMS, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. |
Keywords: first-line chemotherapy, NSCLC, PD-L1, pembrolizumab
PRESS RELEASE
First-line pembrolizumab plus chemotherapy significantly improves outcomes in advanced NSCLC
EMBARGOED until 09 October 2016, 08:15 hours (CEST)
LUGANO-COPENHAGEN, 9 October, 2016 The addition of PD-1 antibody pembrolizumab to standard first-line chemotherapy for treatment-naïve advanced non-small-cell lung cancer significantly improves response rates and progression-free survival, researchers reported at the ESMO 2016 Congress in Copenhagen today (1).
Pembrolizumab is a class of immunotherapeutic anti-cancer drugs called checkpoint inhibitors, which target the mechanism the tumour uses to shut down the body’s immune response.
“Pembrolizumab enables T cells to ‘reactivate’ and accomplish what they are designed to do – facilitate tumour cell killing,” said principal investigator Dr Corey Langer, director of the Thoracic Oncology Program at the Abramson Cancer Center at the University of Pennsylvania, US.
In the phase II KEYNOTE-021 study, researchers randomized 123 patients with stage IIIB/IV, chemotherapy-naive, nonsquamous non-small-cell lung cancer to receive four cycles of carboplatin and pemetrexed (500 mg/m2 every three weeks), with or without 24 months treatment with pembrolizumab (200mg every three weeks).
After a median follow-up of 10.6 months, researchers observed a significantly greater objective response rate (55% vs. 29%, P = 0.0016) in the patients who received pembrolizumab as well as chemotherapy, compared to those treated with chemotherapy alone. While patients were not selected by the amount of PD-L1 expression in their tumour, researchers did note a higher response rate (around 80%) for the pembrolizumab and chemotherapy combination in tumours with PD-L1 expression greater than or equal to 50%.
Participants in the pembrolizumab arm also experienced an improved progression-free survival (median 13.0 months vs. 8.9 months) although overall survival rates were similar between the two arms (6 month survival rate = 92%), in this early landmark assessment.
There was a higher incidence of adverse events of grade 3 severity or above in the pembrolizumab arm compared to the chemotherapy alone arm (39% vs. 26%), but this had no impact on treatment discontinuation rates (10% for the pembrolizumab arm compared to 13% for the chemotherapy only arm) or treatment-related deaths. The most common treatment-related adverse events were fatigue and nausea, which were more common in patients receiving pembrolizumab, and anemia, which was more common in the chemotherapy alone arm of the study.
“This is the first randomized phase II trial in advanced, treatment-naïve non-squamous non-small-cell lung cancer to assess the benefit of adding a monoclonal antibody targeting PD1 to standard chemotherapy,” said Langer. “If these benefits are confirmed in an ongoing phase III trial, the results may radically alter the treatment paradigm in advanced non-small-cell lung cancer.”
Commenting on the study, Dr Raffaele Califano, Consultant in Medical Oncology at The Christie Hospital and University Hospital of South Manchester in Manchester, UK said: “Data for the combination of chemotherapy plus pembrolizumab in this population is certainly encouraging, and it is reassuring to see that the addition of pembrolizumab to first-line chemotherapy has a manageable toxicity profile and doesn’t increase the incidence of treatment-related adverse events or deaths.”
“Notably, the progression-free survival reported in the standard arm was much longer than expected and nearly doubled when compared to historical data, which could be due to patient selection or other clinical/molecular characteristics of the patients enrolled in this study,” Califano said.
“In order to establish if this strategy should be adopted in clinical practice, these results should be investigated further in a phase III randomized study with a similar design, adequately powered for progression-free survival and with robust assessment of patient’s reported outcomes.”
-END-
Notes to Editors
References
1 LBA46_PR - Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-line therapy for advanced NSCLC: KEYNOTE-021 cohort G will be presented by Dr Corey Langer during Presidential Symposium 2 on Sunday 9 October, 16:30 (CEST).
Disclaimer
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .
About the European Society for Medical Oncology
ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.
Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.
LBA46_PR: Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-line therapy for advanced NSCLC: KEYNOTE-021 cohort G
Authors: Corey J. Langer,1 Shirish Gadgeel,2 Hossein Borghaei,3 Vassiliki A. Papadimitrakopoulou,4 Amita Patnaik,5 Steven F. Powell,6 Ryan D. Gentzler,7 Renato G. Martins,8 James P. Stevenson,9 Shadia I. Jalal,10 Amit Panwalkar,11 James Chih-Hsin Yang,12 Matthew Gubens,13 Lecia V. Sequist,14 Mark M. Awad,15 Joseph Fiore,16 Yang Joy Ge,16 Harry Raftopoulos,16 Leena Gandhi15,17
Affiliations: 1Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA; 2Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA; 3Fox Chase Cancer Center, Philadelphia, PA, USA; 4The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5South Texas Accelerated Research Therapeutics, San Antonio, TX, USA; 6Sanford Cancer Center, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA; 7Emily Couric Clinical Cancer Center, University of Virginia School of Medicine, Charlottesville, VA, USA; 8Seattle Cancer Care Alliance, Seattle, WA, USA; 9Cleveland Clinic, Cleveland, OH, USA; 10Indiana University School of Medicine, Indianapolis, IN, USA; 11Sanford Roger Maris Cancer Center, Fargo, ND, USA; 12National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan, Republic of China; 13University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; 14Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA; 15Dana-Farber Cancer Institute, Boston, MA, USA; 16Merck & Co., Inc., Kenilworth, NJ, USA; 17Current affiliation: Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, New York, USA
Background: Pembrolizumab (pembro) monotherapy exhibits robust antitumor activity in PD-L1─expressing advanced NSCLC. Cohort G of the multicenter, open-label, phase 1/2 KEYNOTE-021 study (NCT02039674) evaluated the efficacy and safety of pembro + carboplatin and pemetrexed (CP) vs CP alone as first-line therapy for advanced nonsquamous NSCLC.
Methods: Key eligibility criteria were stage IIIB/IV, chemotherapy-naive, nonsquamous NSCLC, ECOG PS 0-1, and no EGFR mutation or ALK translocation. Patients (pts) were randomized to 4 cycles of carboplatin AUC 5 + pemetrexed 500 mg/m2 Q3W ± 24 mo of pembro 200 mg Q3W; maintenance pemetrexed was allowed in both arms. Randomization was stratified by PD-L1 tumor proportion score ≥1% vs <1%. Eligible pts with radiologic progression on CP could crossover to pembro monotherapy. Primary end point was ORR, with PFS as the key secondary end point; both were assessed per RECIST v1.1 by blinded independent central review. ORR and PFS superiority thresholds were one-sided α = 0.025.
Results: 123 pts were enrolled: 60 in the pembro + CP arm, 63 in the CP arm. Demographics were generally balanced between treatment arms. As of Aug 8, 2016, median follow-up was 10.6 mo (range, 0.8-19.3); median exposure was 8.0 mo for pembro + CP and 4.9 mo for CP. In the CP arm, 43 pts discontinued therapy; 32 received subsequent anti–PD-1 therapy as part of crossover (n = 20) or off study (n = 12). Pembro + CP significantly improved ORR (55% vs 29%; P = 0.0016) and PFS (HR 0.53, 95% CI 0.31-0.91, P = 0.0102; median 13.0 vs 8.9 mo). Overall survival was similar; 6-mo survival rates were 92% in each arm. Without adjusting for exposure, for pembro + CP vs CP, treatment-related AEs led to discontinuation in10% vs 13%, were of grade ≥3 severity in 39% vs 26%, and led to death in 2% (sepsis, n = 1) vs 3% (sepsis and pancytopenia, n = 1 each). The most common any-grade treatment-related AEs were fatigue (64% vs 40%), nausea (58% vs 44%), and anemia (32% vs 53%).
Conclusions: Pembro 200 mg Q3W + CP demonstrated a statistically significant, clinically relevant ORR and PFS benefit over CP alone and had a manageable, safety profile as first-line therapy in patients with advanced nonsquamous NSCLC.
PRESS RELEASE
EMBARGOED until 9 October 2016, 08:15 hours (CEST)
Ceritinib provides longer progression-free survival than chemotherapy in phase III trial of ALK rearranged lung cancer treatment
LUGANO-COPENHAGEN, 9 October, 2016 – Ceritinib provides longer progression-free survival than chemotherapy in crizotinib-pre-treated patients with non-small-cell lung cancer harbouring an ALK rearrangement, according to results of the phase III ASCEND-5 study presented today at the ESMO 2016 Congress in Copenhagen.1
“Patients with non-small cell lung cancer (NSCLC) should receive front line therapy with the anaplastic lymphoma kinase (ALK) inhibitor crizotinib,” said lead author Professor Giorgio Scagliotti, head of the Department of Oncology, University of Turin, Italy. “Most patients develop resistance to crizotinib and currently second line treatment is represented by chemotherapy alone.”
He continued: “This was the first phase III study to assess whether the second generation ALK inhibitor ceritinib was superior to chemotherapy upon progression on crizotinib therapy in NSCLC.”
The open-label ASCEND-5 study included 231 patients with NSCLC who had received crizotinib. Patients were randomised 1:1 to receive therapy with ceritinib or chemotherapy (pemetrexed or docetaxel). Patients who discontinued chemotherapy due to disease progression could crossover to ceritinib. The primary endpoint was progression-free survival, assessed by a blinded independent review committee.
Median progression-free survival was significantly improved with ceritinib compared to chemotherapy (5.4 vs 1.6 months, hazard ratio [HR] 0.49, p<0.001). Ceritinib increased overall response rate compared to chemotherapy (39.1% vs 6.9%). There was no improvement in overall survival with ceritinib compared to chemotherapy.
Of the patients who discontinued chemotherapy due to disease progression, 75 crossed over to ceritinib.
Scagliotti said: “Progression-free survival was significantly lengthened with ceritinib compared to chemotherapy. We did not observe an improvement in overall survival with ceritinib, probably because the patients who crossed over diluted the potential benefit.”
Patients taking ceritinib had similar toxicities to those observed in phase I and II studies. The most frequent grade 3/4 adverse events with ceritinib were nausea (7.8%), vomiting (7.8%) and diarrhoea (4.3%), and with chemotherapy were neutropaenia (15.5%), fatigue (4.4%) and nausea (1.8%). Ceritinib significantly improved patient-reported outcomes including lung cancer-specific symptoms and overall health status, compared to placebo (p<0.05).
“This study opens up a new treatment paradigm after crizotinib failure,” said Scagliotti. “It would be logical now to give a sequence of active drugs, starting with crizotinib in first line and moving to ceritinib in second line.”
Commenting on the trial, Dr Alice Shaw, director of thoracic oncology at the Massachusetts General Hospital Cancer Centre in Boston, US, said: “This is the first randomised study to examine how a second generation ALK inhibitor compares to standard second line chemotherapy in ALK positive patients who failed the standard first line therapy, which currently is crizotinib.”
“Single arm studies have suggested that ceritinib and alectinib could be standard options in the second line setting after crizotinib has failed,” continued Shaw. “But the positive effect on progression-free survival in this phase III study confirms that there is greater benefit using a second ALK inhibitor over standard chemotherapy. This will establish sequential crizotinib followed by a second generation ALK inhibitor as the standard treatment for patients with metastatic ALK positive lung cancer.”
She concluded: “We are now waiting on the results of trials testing the second generation ALK inhibitors ceritinib (versus chemotherapy) and alectinib (versus crizotinib) in the first line setting. The latter trial addresses one of the most fundamental questions in the field, which is what should be the first ALK inhibitor that patients receive.”
-END-
Notes to Editors
References
1 Abstract LBA42_PR ‘Ceritinib vs chemotherapy (CT) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with CT and crizotinib (CRZ): results from the confirmatory phase 3 ASCEND-5 study,‘will be presented by Dr Giorgio Scagliotti during the Proffered Paper Session NSCLC, metastatic 1 on Sunday, 9 October 2016, 11:00 to 12:30 (CEST) in Room Copenhagen.
Disclaimer
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .
About the European Society for Medical Oncology
ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.
Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.
Abstract for LBA42_PR
Ceritinib vs chemotherapy (CT) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously treated with CT and crizotinib (CRZ): results from the confirmatory phase 3 ASCEND-5 study
G. Scagliotti1, T.M. Kim2, L. Crinò3, G. Liu4, C. Gridelli5, S. Novello1, K. Kiura6, A. Bearz7, O. Gautschi8, E. Felip9, M. Nishio10, D.R. Spigel11, T.S.K. Mok12, P. Urban13, S. Deudon13, C. Zheng14, A.T. Shaw15
1Department of Oncology, University of Torino, Turin, Italy, 2Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, 3Medical Oncology, University Medical School of Perugia, Perugia, Italy, 4Medicine, Princess Margaret Cancer Centre, Toronto, ON, Canada, 5Medical Oncology, SG Moscati Hospital, Avellino, Italy, 6Department of Allergy and Respiratory Medicine (Thoracic Oncology), Okayama University Hospital, Okayama, Japan, 7Division of Medical Oncology, IRCCS-CRO, Aviano, Italy, 8Department of Medicine, Medical Oncology, Cantonal Hospital Lucerne, Lucerne, Switzerland, 9Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain, 10Thoracic Medical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan, 11Medical Oncology, Sarah Cannon Research Institute, Nashville, TN, USA, 12Clinical Oncology, Chinese University of Hong Kong, Shatin, China, 13Clinical Research, Novartis Pharma AG, Basel, Switzerland, 14Biostatistics, Novartis Pharma, East Hanover, NJ, USA, 15Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA, USA
Background: The ALK inhibitor CRZ is effective in ALK+ NSCLC pts, but most develop resistance and progressive disease (PD). Ceritinib showed robust efficacy in CRZ-pretreated pts in phase 1 & 2 studies. This multicenter, open-label phase 3 study (NCT01828112) compared efficacy of ceritinib vs CT in ALK+ NSCLC pts pretreated with CT & CRZ.
Methods: ALK+ NSCLC pts pretreated with 1–2 CT regimens & CRZ were randomized to oral ceritinib 750 mg/d or CT (pemetrexed [PEM] 500 mg/m2 or docetaxel [DOC] 75 mg/m2), stratified by WHO PS (0 vs 1–2) & brain metastasis at screening. Pts discontinuing CT due to PD could crossover to ceritinib. Primary endpoint was progression-free survival (PFS), assessed by blinded independent review committee (BIRC) per RECIST v1.1.
Results: Of 231 pts (median age 54 y), 115 were randomized to ceritinib and 116 to CT (PEM, n=40; DOC, n=73; 3 not treated). Median treatment exposure was 30.3 wk for ceritinib and 6.3 wk for CT. Median follow-up duration was 16.5 mo. Ceritinib showed statistically significant improvement in PFS (BIRC: median 5.4 vs 1.6 mo, HR=0.49, P<0.001) and increased overall response rate [95% CI] (BIRC: 39.1% [30.2, 48.7] vs 6.9% [3.0, 13.1]) vs CT (Table). Of pts discontinuing CT due to PD, 75 crossed over to ceritinib. Most frequent AEs (% any grade [% grade 3/4]) were diarrhoea (72.2 [4.3]), nausea (66.1 [7.8]) & vomiting (52.2 [7.8]) with ceritinib; fatigue (28.3 [4.4]), nausea (23.0 [1.8]), alopecia (21.2 [0]) & neutropenia (20.4 [15.0]) with CT. 6 (5.2%) ceritinib- and 8 (6.9%) CT-treated pts discontinued due to AEs. Ceritinib significantly improved lung cancer-specific symptoms (LCSS & QLQ-LC13) & overall health status (EQ-5D) vs CT (P<0.05). Table
|
|
Ceritinib(n=115) |
CT(n=116) |
|
By BIRC |
|
|
|
Median PFS, mo [95% CI] |
5.4* [4.1, 6.9] |
1.6 [1.4, 2.8] |
|
ORR (CR+PR), % [95% CI] |
39.1 [30.2, 48.7] |
6.9 [3.0, 13.1] |
|
DCR (CR+PR+SD), % [95% CI] |
76.5 |
36.2[27.5, 45.6] |
|
By Investigator |
|
|
|
Median PFS, mo [95% CI] |
6.7* |
1.6 |
|
ORR (CR+PR), % [95% CI] |
42.6 [33.4, 52.2] |
6.0 |
|
DCR (CR+PR+SD), % [95% CI] |
80.0 |
37.9 [29.1, 47.4] |
|
Median OS, mo [95% CI] |
18.1† |
20.1[11.9, 25.1] |
|
*Log-rank P<0.001 vs CT |
|
|
Conclusions: Ceritinib showed a clinically meaningful and statistically significant improvement in PFS vs CT in pretreated ALK+ NSCLC.
Clinical trial identification: NCT01828112
Legal entity responsible for the study: Novartis Pharmaceutical Corporation
Funding: Novartis Pharmaceutical Corporation
|
Disclosure: |
G. Scagliotti: Honoraria: Eli Lilly, AZ, Pfizer, Roche, Clovis Oncology Consulting/advisory, Speaker fees: Eli Lilly Travel/accommodation/expenses: Bayer. |
Keywords: ALK positive, ALK pretreated, NSCLC, Ceritinib
PRESS RELEASE
EMBARGOED until 9 October 2016, 08:15 hours (CEST)
Greater patient selection may be needed for first line nivolumab to improve progression-free survival in advanced lung cancer
LUGANO-COPENHAGEN, 9 October, 2016 – Greater patient selection may be needed for first line nivolumab to improve progression-free survival over chemotherapy in advanced lung cancer as the CheckMate 026 trial gave negative results in a broad group of patients expressing PD-L1 in their tumour cells. The findings were presented at the ESMO 2016 Congress in Copenhagen.1
“Nivolumab represents a standard of care in the second-line treatment of advanced non-small cell lung cancer (NSCLC) as it improved overall survival compared to docetaxel in phase III trials in these patients,” said lead author Dr Mark A. Socinski, Executive Medical Director, Florida Hospital Cancer Institute, US.2,3
“In the first line setting, nivolumab showed a promising response rate in a phase I trial in advanced NSCLC patients with 1% or greater PD-L1 expression in their tumour cells,” he continued.4
The phase III CheckMate 026 trial investigated the efficacy of first line treatment with nivolumab compared to platinum-based doublet chemotherapy in patients with advanced NSCLC and PD-L1 positive tumours (defined as present in 1% or more tumour cells). Patients with EGFR activating mutations and ALK translocations, which are sensitive to targeted therapy, were excluded. The primary endpoint was progression-free survival, assessed by an independent radiology review committee in patients with PD-L1 in 5% or more tumour cells.
A total of 541 patients were randomised 1:1 to nivolumab or chemotherapy. Patients who progressed on chemotherapy could crossover to nivolumab as second line treatment.
In the 423 patients with 5% or greater PD-L1 expression, progression-free survival was 4.2 months with nivolumab and 5.9 months with chemotherapy (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.91–1.45, p=0.25). Overall survival was 14.4 months for nivolumab versus 13.2 months for chemotherapy (HR 1.02, 95% CI 0.80–1.30). Among all treated patients, any and serious treatment-related adverse events were 71% and 18% with nivolumab, and 92% and 51% with chemotherapy, respectively.
“There were no new safety signals with nivolumab and it was less toxic than chemotherapy,” said Socinski.
“There are a number of possible reasons for the disappointing progression-free survival results,” he added. “Regarding overall survival, there was a high rate of crossover to immunotherapy on the chemotherapy arm. Overall survival in the chemotherapy arm was better than historical standards, which could be due to the fact that it had a greater proportion of women and Asian patients. We are conducting further analyses to evaluate these results.”
“Platinum-based chemotherapy is the standard first line treatment because it makes patients live longer and palliates symptoms,” said Socinski. “If we are going to replace it with immunotherapy, we need to be confident that we are identifying the patients who will derive greater benefit.”
Socinski concluded: “Combination immunotherapies may increase the proportion of patients who benefit in the first line. The phase III CheckMate 227 trial is investigating treatment with nivolumab plus ipilimumab in the first line setting relative to standard chemotherapy.”
Commenting on the results, Professor Johan Vansteenkiste, Professor of Medicine, Catholic University Leuven, and Chief Oncology Physician, Unit of Respiratory Oncology, University Hospital KU Leuven, Belgium, said: “Nivolumab did not improve progression-free survival over chemotherapy in this study. In my view the reason is because the trial included a broad range of patients with a low PD-L1 expression threshold of just 1% or greater. Standard first line treatment with platinum doublet chemotherapy gives a progression-free survival of six months and to beat that may require being more selective on who receives the drug.”
He continued: “More research is needed about how to use the PD-L1 biomarker to select patients for treatment with nivolumab. In addition, phase I studies suggest that combination immunotherapy improves response rate and outcome, but at the expense of increased toxicity, compared to single agent immunotherapy in NSCLC. So, it will be important to investigate this strategy further.”
-END-
Notes to Editors
References
1 Abstract LBA7_PR ‘CheckMate 026: A Phase 3 Trial of Nivolumab vs Investigator's Choice (IC) of Platinum-Based Doublet Chemotherapy (PT-DC) as First-Line Therapy for Stage IV/Recurrent Programmed Death Ligand 1 (PD-L1) − Positive NSCLC’ will be presented by Dr Mark Socinski during the Presidential Symposium 2 on Sunday, 9 October, 2016 16:25 to 18:20 (CEST) in Room Copenhagen.
2 Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 20159;373(2):123–135. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.
3 Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627–1639. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.
4 Gettinger S, Rizvi NA, Chow LQ, et al. Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2016;34(25):2980–2987. doi: 10.1200/JCO.2016.66.9929. Epub 2016 Jun 27.
Disclaimer
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .
About the European Society for Medical Oncology
ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.
Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.
Abstract for LBA7_PR
CheckMate 026: A Phase 3 Trial of Nivolumab vs Investigator's Choice (IC) of Platinum-Based Doublet Chemotherapy (PT-DC) as First-Line Therapy for Stage IV/Recurrent Programmed Death Ligand 1 (PD-L1) − Positive NSCLC
M. Socinski1, B. Creelan2, L. Horn3, M. Reck4, L. Paz-Ares5, M. Steins6, E. Felip7, M. van den Heuvel8, T.E. Ciuleanu9, F. Badin10, N. Ready11, T.J.N. Hiltermann12, S. Nair13, R. Juergens14, S. Peters15, E. Minenza16, W.J. Geese17, P. Bhagavatheeswaran18, A. Chen19, D.P. Carbone20
1Medical Oncology, UPMC Cancer Center, Pittsburgh, PA, USA, 2Thoracic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA, 3Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA, 4Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Grosshansdorf, Germany, 5Medical Oncology, Hospital Universitario Doce de Octubre & CNIO, Madrid, Spain, 6Oncology, Thoraxklinik-Heidelberg gGmbH, Heidelberg, Germany, 7Oncologia Médica, Hospital Universitari Vall d’Hebron, Barcelona, Spain, 8Thoracic Oncology, Antoni Van Leeuwenhoek Ziekenhuis, Amsterdam, Netherlands, 9Medical Oncology, Prof. Dr. Ion Chiricuta Institute of Oncology and UMF Iuliu Hatieganu, Cluj-Napoca, Romania, 10Oncology, Baptist Health Lexington, Lexington, KY, USA, 11Oncology, Duke University Medical Center, Durham, NC, USA, 12Pulmology Oncology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands, 13Hematology-Medical Oncology, Lehigh Valley Health Network, Allentown, PA, USA, 14Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada, 15Oncology, University of Lausanne, Lausanne, Switzerland, 16Oncology, Ospedale S. Maria Nuova, Terni, Italy, 17Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 18Global Biometric Sciences, Bristol-Myers Squibb, Princeton, NJ, USA, 19Global Clinical Research Oncology, Bristol-Myers Squibb, Princeton, NJ, USA, 20Department of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
Background: Nivolumab improves OS compared with docetaxel in previously treated NSCLC. In a phase 1 study (CheckMate 012), nivolumab showed promising activity and manageable safety as monotherapy and in combination with ipilimumab in treatment naive advanced NSCLC. CheckMate 026 (NCT02041533), an open-label, randomized phase 3 study, evaluated the efficacy of nivolumab vs IC PT-DC as first-line therapy in stage IV/recurrent PD-L1−positive NSCLC.
Methods: Patients with histologically confirmed and previously untreated stage IV or recurrent NSCLC, ECOG PS 0−1, and PD-L1 positivity were randomized 1:1 to receive nivolumab 3 mg/kg IV Q2W or IC PT-DC (histology-based) Q3W (up to 6 cycles) until disease progression or unacceptable toxicity. Patients with EGFR/ALK mutations sensitive to targeted therapy were excluded. Patients on IC PT-DC could crossover to nivolumab upon progression. The primary objective was comparison of PFS (per RECIST 1.1) as assessed by an independent radiology review committee in patients with ≥5% PD‑L1 tumor expression at randomization.
Results: A total of 541 patients were randomized to treatment. In patients with ≥5% PD-L1 expression (n = 423), nivolumab did not improve PFS (HR, 1.15; 95% CI 0.91 to 1.45; P=0.25). Median PFS was 4.2 mo and 5.9 mo with nivolumab and IC PT-DC, respectively. Among all treated patients, any grade and grade 3/4 treatment-related adverse events were 71% and 18% with nivolumab, as compared to 92% and 51% with IC PT-DC, respectively. Secondary endpoints including PFS in all randomized patients, OS, and ORR will be presented.
Conclusions: Nivolumab did not show superior PFS compared to IC PT-DC as first-line therapy in stage IV/recurrent NSCLC patients with ≥5% PD-L1 tumor expression. The safety profile of nivolumab was favorable to IC PT-DC and consistent with previous studies. Nivolumab plus ipilimumab and nivolumab plus chemotherapy are being evaluated in a phase 3 trial in previously untreated NSCLC (CheckMate 227).
Clinical trial identification: NCT02041533
Legal entity responsible for the study: Bristol-Myers Squibb
Funding: Bristol-Myers Squibb
|
Disclosure: |
B. Creelan: Honoraria and research funding from Boehringer-Ingelheim. Received Speakers’ Bureau payment and Travel, Accommodations, and Expenses from Bristol-Myers Squibb and AstraZeneca |
Keyword: nivolumab, metastatic NSCLC, first-line, PD-L1
PRESS RELEASE
EMBARGOED until 9 October 2016, 08:15 hours (CEST)
Nintedanib improves progression-free survival but not overall survival in phase III trial of metastatic colorectal cancer
LUGANO-COPENHAGEN, 9 October, 2016 – Nintedanib improves progression-free survival but not overall survival in patients with metastatic colorectal cancer who are not responding to standard therapies, according to results of the phase III LUME-colon 1 trial presented at the ESMO 2016 Congress in Copenhagen.1
“Colorectal cancer is a frequent disease and a large proportion of patients have metastases,” said lead author Professor Eric Van Cutsem, head of Clinical Digestive Oncology at University Hospitals Leuven, Belgium. “Many patients progress to several different lines of treatment and then stop responding. There is a need to find new therapies for this big group of patients.”
Nintedanib is a multiple tyrosine kinase inhibitor with anti-angiogenic activity. LUME-colon 1 was the first phase III trial of nintedanib in patients with metastatic colorectal cancer refractory to all available treatments including chemotherapy and biological therapies. Patients had to be in good general condition (defined as performance status 0 and 1) and have good organ function.
The trial included 768 patients who were randomised 1:1 to nintedanib or placebo. All patients received best supportive care. The co-primary endpoints were progression-free survival and overall survival.
Nintedanib significantly improved median progression-free survival compared to placebo (1.5 vs 1.4 months, hazard ratio 0.58, 95% confidence interval [CI] 0.49–0.69, p<0.0001). There was no difference in overall survival between the two groups.
Disease control was improved with nintedanib compared to placebo (26% vs 11%, odds ratio 2.96, 95% CI 2.00–4.4, p<0.0001). Serious adverse events occurred in 39% of patients taking nintedanib and 35% on placebo. Some 14% of patients in the nintedanib group discontinued treatment due to adverse events, compared to 11% in the placebo group.
Van Cutsem said: “Nintedanib was well tolerated and gave a significant increase in progression-free survival which means that tumours stopped growing more frequently in patients taking the drug. But patients receiving nintedanib did not live longer, which was disappointing.”
“The reason why patients on placebo survived longer than expected is not completely clear, but treatments taken after the trial that stopped their tumour from growing may have contributed to this finding,” continued Van Cutsem. “After the trial finished, patients were followed until death and these subsequent treatments may have diluted the effect of nintedanib, leading to a loss in potential survival benefit.”
He concluded: “We are conducting additional analyses in molecular markers and subtypes of colorectal cancer to see if there is a group of patients who benefit from nintedanib after other therapies have failed.”
Commenting on the findings, Dr. Dirk Arnold, Instituto CUF de Oncologia, Lisbon, Portugal, said: “Having another of those large trials in this specific setting clearly indicates the unmet need. Nintedanib shows good tolerability but the efficacy results are somehow disappointing.”
“Nintedanib delays disease progression and increases the rate of stable disease but these gains are lost when it comes to overall survival,” continued Arnold. “This is in contrast to regorafenib and trifluridine/tipiracil which both showed increases in both progression-free survival and overall survival in this line of treatment.”
“The disparity could be because more patients who progressed in the LUME-colon 1 trial received salvage treaments than in the earlier trials,” he added. “The relatively long overall survival also of patients with placebo in the current trial supports this hypothesis. Also, by contrast to the other trials, quite a lot of patients already underwent treatment for this late-line situation before. Another possibility could be that nintedanib simply doesn’t work well enough, since both regorafenib and trifluridine/tipiracil also had somewhat larger effects on progression-free survival.”
Arnold concluded: “More data is needed to explain the findings and understand how strong the benefit of nintedanib really is.”
-END-
Notes to Editors
References
1 Abstract LBA20_PR ‘Nintedanib plus best supportive care (BSC) versus placebo plus BSC for the treatment of patients (pts) with colorectal cancer (CRC) refractory to standard therapies: Results of the phase III LUME-colon 1 study‘ will be presented by Professor Eric Van Cutsem during the Proffered Paper Session, Gastrointestinal tumours, colorectal 1 on Sunday, 9 October 2016, 14:45 to 16:15 (CEST) in Room Vienna.
Disclaimer
This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .
About the European Society for Medical Oncology
ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.
Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.
Abstract for LBA20_PR Nintedanib plus best supportive care (BSC) versus placebo plus BSC for the treatment of patients (pts) with colorectal cancer (CRC) refractory to standard therapies: Results of the phase III LUME-colon 1 study
E. Van Cutsem1, T. Yoshino2, H-J. Lenz3, S. Lonardi4, A. Falcone5, M.L. Limon6, M.P. Saunders7, A. Sobrero8, E. Maiello9, Y.S. Park10, R. Ferreiro Monteagudo11, Y.S. Hong12, J. Tomasek13, H. Taniguchi14, F. Ciardiello15, J. Hocke16, Z. Oum’hamed17, S. Vlassak18, M. Studeny19, J. Tabernero20
1Digestive Oncology, University Hospitals Leuven - Campus Gasthuisberg, Leuven, Belgium, 2Department of GI Oncology, National Cancer Center Hospital East, Kashiwa, Japan, 3Department of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 4Oncologia Medica 1, Istituto Oncologico Veneto IRCCS, Padua, Italy, 5Oncologia Medica, Azienda Ospedaliera Universitaria S.Chiara, Pisa, Italy, 6Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain, 7Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK, 8Department of Medical Oncology, Ospedale S. Martino, Genoa, Italy, 9Onco-Hematology, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy, 10Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 11Medical Oncology, Hospital Universitario Ramon y Cajal, Madrid, Spain, 12Department of oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 13Medical Communications, InVentiv Health, London, UK, 14Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, 15Medical Oncology, AOU Seconda Università degli Studi di Napoli (AOU-SUN), Naples, Italy, 16Statistics, Boehringer Ingelheim Pharma GmbH & Co. KG, Tübingen, Germany, 17Clinical Trials, Boehringer Ingelheim B.V. France S.A.S, Reims, France, 18Medical Affairs, SCS Boehringer Ingelheim Comm. V., Brussels, Belgium, 19Division of Medicine/Clinical Development Department, Boehringer Ingelheim, Vienna, Austria, 20Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, Barcelona, Spain
Background: Angiogenesis is critical to CRC tumour growth and metastasis. Nintedanib (N) is a multiple angiokinase signalling pathway inhibitor (including VEGFR, PDGFR and FGFR). N demonstrated similar efficacy to bevacizumab when combined with mFOLFOX6 as 1st-line therapy in a Phase I/II study. These findings and a manageable safety profile provided the rationale to examine N in refractory CRC. We conducted a global, randomised Phase III study (NCT02149108) to evaluate the efficacy and safety of N in pts with mCRC after failure of standard therapies.
Methods: Eligible pts (aged ≥18 years; ECOG PS 0–1; mCRC adenocarcinoma refractory to standard treatments, including oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF and anti-EGFR in RAS wt) were randomised 1:1 to receive either N (200 mg bid) + BSC or placebo (P; bid) + BSC. The co-primary endpoints were PFS by central review and OS, evaluated by log-rank test to determine the effect of N independently at the two-sided alpha level of 0.05.
Results: 768 mCRC patients (37% pretreated with regorafenib) were randomised to N (n=386) or P (n=382). Baseline characteristics were similar between the groups. A statistically significant improvement in PFS was observed (HR [95% CI] 0.58 [0.49, 0.69]; p<0.0001; median PFS 1.5 months with N vs 1.4 months with P), but no difference in OS (HR [95% CI]: 1.01 [0.86, 1.19]; p=0.8659; median OS 6.4 months with N vs 6.1 months with P). Disease control by central review was 26% with N vs 11% with P (OR [95% CI]: 2.96 [2.00, 4.4]; p<0.0001). 14% of patients in the N arm discontinued due to AEs, vs 11% with P. Serious AEs occurred in 39% vs 35% of patients in the N and P arms, respectively. The most frequent ≥Grade 3 AEs (in the N arm, by medical concept) occurring in N vs P patients were liver related investigations (16% vs 8%) and fatigue (9% vs 6%).
Conclusions: N was well tolerated and demonstrated clinical activity, with a significant increase in PFS (HR 0.58). However, improvement in PFS did not translate to an improvement in OS. Additional analyses are ongoing to further interrogate the efficacy findings.
Clinical trial identification: NCT02149108
Legal entity responsible for the study: Boehringer Ingelheim GmbH & Co. KG
Funding: Boehringer Ingelheim GmbH & Co. KG
|
Disclosure: |
E. Van Cutsem: Research funding paid to his institute from Amgen; Bayer; Boehringer Ingelheim; Lilly; Merck Serono; Novartis; Roche and Sanofi. |
Keywords: angiogenesis inhibition, NINTEDANIB, colorectal cancer