ДУ "Інститут урології
імені академіка О.Ф.Возіанова"

EMBARGOED until 15 April 2016, 09:00 AM hours (CEST)

Patients with EGFR expressing non-small-cell lung cancer benefit most from necitumumab added to chemotherapy

Presentation at the European Lung Cancer Conference (ELCC)

GENEVA, Switzerland, 15 April 2016 – Patients with epidermal growth factor receptor (EGFR) expressing advanced squamous non-small-cell lung cancer benefit most from necitumumab added to gemcitabine and cisplatin chemotherapy, according to a subgroup analysis from the SQUIRE trial presented today at the European Lung Cancer Conference (ELCC) 2016 in Geneva, Switzerland.1

The randomised phase III SQUIRE trial demonstrated that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improved overall survival in patients with stage IV squamous non-small-cell lung cancer by 1.6 months compared to chemotherapy alone. The current study analysed outcomes in the subgroup of patients with EGFR expressing tumours  compared to those with no EGFRs.

Out of 982 patients in the SQUIRE trial, 95% had EGFR expressing tumours and 5% had tumours with no EGFR protein. The addition of necitumumab to gemcitabine and cisplatin chemotherapy improved overall survival and progression free survival by 21% and 16%, respectively, as compared to chemotherapy alone in patients whose tumours expressed the EGFR protein. There was no benefit in patients with no EGFR in their tumours.

Dr Luis Paz-Ares, Chief of medical oncology at the University Hospital 12 De Octubre in Madrid, Spain, lead author, said: “Necitumumab is targeted at EGFR so it makes sense that the drug is active in patients with the receptor. Our analysis showed that the drug had no effect when the receptor was absent, presumably because there was no target to bind to. We cannot make robust conclusions because the subgroup of patients with negative EGFR was very small, but the hypothesis generated here is that those tumours do not respond well to necitumumab.”

“Based on this analysis, the European Medicines Agency has decided that necitumumab is approved only for patients with EGFR expressing tumours,” continued Paz-Ares. “On the other hand the US Food and Drug Administration has taken the more conservative approach which recognises that SQUIRE was designed for all-comers without prior selection, and this subgroup analysis is insufficient evidence to conclude that patients with EGFR negative tumours are not candidates.”

He concluded: “Our results need to be interpreted with caution. A confirmatory study in patients with EGFR negative tumours is needed to assess whether they are good candidates for necitumumab or not.”

Commenting on the findings, Prof Robert Pirker, programme director for lung cancer at the Vienna General Hospital in Vienna, Austria, not involved in the study, said: “This subgroup analysis shows that the effect of necitumumab was slightly greater in patients with EGFR expressing tumours than it was in the entire SQUIRE population. It indicates that immunohistochemical detection of the EGFR receptor improves clinical activity of necitumumab. The findings are consistent with previous studies suggesting that monoclonal antibodies in combination with chemotherapy work better in patients with EGFR expressing cells.”

Pirker added that a more thorough analysis is needed. He said: “Information on outcome of patients with cut-off levels higher than in the current analysis would be of interest. We also need to know the effect of necitumumab according to both percentages of positive cells and their staining intensity. This could be combined with fluorescence in situ hybridisation (FISH) analysis to detect gene amplification. This could give us a clearer picture of which patients benefit most from necitumumab.”

-END-

References

1 132O_PR: Subgroup analyses of patients with epidermal growth factor receptor (EGFR)-expressing tumors in SQUIRE: A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) plus necitumumab (N) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). L. Paz-Ares, Spain. Friday 15th April 2016 – 09:00-09:15 NSCLC targeted therapy and circulating biomarkers Room C

Notes to Editors

Disclaimer

Information contained in this press release was provided by the lecture authors. It does not necessarily express ESMO's or IASLC’s point of view.

About the European Lung Cancer Conference (ELCC) 2016

The European Lung Cancer Conference (ELCC) has become the reference event in Europe for professionals treating lung cancers. It is organized by the European Society for Medical Oncology and the International Association for the Study of Lung Cancer, in collaboration with the partner societies ESTRO, ESTS and ETOP.

ELCC provides a comprehensive multidisciplinary overview of the latest as well as of the state-of-the-art knowledge in thoracic malignancies, covering different aspects such as prevention, screening, diagnosis, treatment modalities and the results of basic, clinical and translational research, presented by top international academic experts. Around 2,000 attendees are expected from throughout Europe and the rest of the world.

About the European Society for Medical Oncology

ESMO is the leading professional organisation for medical oncology. With more than 14,000 members representing oncology professionals from over 130 countries, ESMO is the society of reference for oncology education and information.

ESMO’s educational resources support an integrated, multi-professional approach to cancer care. We have European roots and a global

reach: we welcome oncology professionals from around the world and we seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.

To learn about ESMO, visit www.esmo.org

About International Association for the Study of Lung Cancer
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer. Founded in 1974, the association’s membership includes more than 5,000 lung cancer specialists in over 100 countries. IASLC members promote the study of etiology, epidemiology, prevention, diagnosis, treatment and all other aspects of lung cancer and thoracic malignancies. IASLC brings scientists, members of the medical community and the public together from all over the world to share best practices and discover new and better ways to eliminate the health threat of thoracic cancers. Membership is open to any physician, scientist, nurse or allied health professional interested in lung cancer and other thoracic malignancies, including patients, survivors, caregivers and advocates. Visit www.iaslc.org for more information and follow us on Twitter @IASLC

Abstract 132O _PR

Subgroup analyses of patients with epidermal growth factor receptor (EGFR)-expressing tumors in SQUIRE: A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) plus necitumumab (N) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC)

L. Paz-Ares1, M.A. Socinski2, J. Shahidi3, R.R. Hozak4, V. Soldatenkova5, N. Thatcher6, F. Hirsch7 
1Department of Medical Oncology, University Hospital 12 De Octubre, Madrid, Spain, 2Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA, 3Oncology, Eli Lilly and Company, Bridgewater, NJ, USA, 4Oncology, Eli Lilly and Company, Indianapolis, IN, USA, 5Oncology, Eli Lilly and Company, Bad Homburg, Germany, 6Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK, 7Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

Background: SQUIRE demonstrated addition of N to GC significantly improved survival in pts with stage IV sq-NSCLC. Here we present SQUIRE trial outcomes for the patient sub-population with EGFR-expressing tumors.

Methods: Pts with pathologically confirmed stage IV sq-NSCLC were randomized 1:1 to GC (G=1250 mg/m² iv, days 1 and 8; C=75 mg/m² iv, day 1) plus N (800 mg iv, days 1 and 8) (GC+N arm), or GC alone (GC arm) every 21 days for up to 6 cycles. GC+N pts with no progression continued on N alone until progressive disease or intolerable toxicity. SQUIRE included mandatory tissue collection. EGFR protein expression was assessed by IHC in a central lab, using Dako EGFR PharmDx kit. Exploratory analyses were pre-specified for pts with EGFR-expressing (EGFR>0) and non-expressing (EGFR=0) tumors. Subgroup analyses using separate stratified models are presented.

Results: 982 patients (89.8% of ITT) had evaluable IHC assay results. The large majority of these pts (95.2%) had tumor samples expressing EGFR protein; 4.8% had tumors without detectable EGFR protein. Baseline characteristics for EGFR>0 patients were well-balanced between GC+N and GC. HRs (GC+N vs. GC) for OS and PFS in pts with EGFR>0 were 0.79 (95% CI: 0.69-0.92, p=0.002) and 0.84 (95% CI: 0.72-0.97, p=0.018). For EGFR=0, corresponding HRs were 1.52 (95% CI: 0.74-3.12, p=0.253) and 1.33 (95% CI: 0.65-2.70, p=0.428). EGFR expression across the range of IHC values did not identify another meaningful cut-point. Post-progression anticancer therapy for EGFR>0 pts was similar between arms (49% vs 47%). All

pre-specified subgroups showed an OS benefit in EGFR>0 pts. Grade ≥3 adverse events in EGFR>0 pts for GC+N that showed a >3% increase over GC were hypomagnesemia (9.6% vs 0.9%) and skin rash (6.4% vs 0.4%).

Conclusions: Similar to SQUIRE ITT, the sub-population of pts with EGFR-expressing advanced sq-NSCLC benefitted from the addition of N to GC; the safety profile was consistent with that of the overall SQUIRE population.

Clinical trial identification: NCT00981058

Legal entity responsible for the study: N/A

Funding: Eli Lilly and Company

Keywords: EGFR expressing, squamous NSCLC, necitumumab, SQUIRE phase III trial