1312P - The relationship between EGFR and KRAS mutation status and overall survival (OS) in the NCIC CTG BR.26 randomized trial of dacomitinib (D) versus p...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Peter Ellis
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors P.M. Ellis1, G. Liu2, M. Millward3, F. Perrone4, F.A. Shepherd5, L.K. Seymour6, S. Sun7, B. Cho8, A. Morabito9, M. Stockler10, N. Leighl2, C. Lee11, R. Wierzbicki12, A. Favaretto13, M. Tsao14, C.F. Wilson6, I. Taylor15, K. Ding6, G. Goss16, P.A. Bradbury6
  • 1Medical Oncology, Jurvainski Cancer Centre, L8V 5C2 - Hamilton/CA
  • 2Department Of Medical Oncology, Princess Margaret Hospital, University Health Network, M5G 2M9 - Toronto/CA
  • 3Medical Oncology, Australasian Lung cancer Trials Group, Perth/AU
  • 4Medical Oncology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Naples/IT
  • 5Dept. Of Medical Oncology (suite 5-104, Zip M1m 3p4), Princess Margaret Hospital, M5G 2C4 - Toronto/CA
  • 6Ncic Clinical Trials Group, Queen's University, Kingston/CA
  • 7Medical Oncology, British Columbia Cancer Agency, vancouver/CA
  • 8Division Of Oncology, Department Of Internal Medicine, Yonsei University, College of Medicine, 120-752 - Seoul/KR
  • 9Medical Oncology, Istituto Nazionale Tumori di Napoli, Naples/IT
  • 10Medical Oncology, NHMRC Clinical Trials Group, Sydney/AU
  • 11Fraser Valley Cancer Centre, British Columbia Cancer Agency, Surrey/CA
  • 12Oncology, RS McLaughlan Durham Regional Cancer Centre, Oshawa/CA
  • 13Oncologia Medica 2, Istituto Oncologico Veneto IOV-IRCCS, IT-35128 - Padova/IT
  • 14Pathology Department, Princess Margaret Cancer Centre, Toronto/CA
  • 15Translational Oncology, Pfizer Inc, Groton/US
  • 16Medical Oncology, The Ottawa Hospital Cancer Centre, K1H 8L6 - Ottawa/CA

Abstract

Aim

Dacomitinib (D) is an irreversible, pan Her inhibitor with activity in NSCLC previously treated with an EGFR TKI.

Methods

BR26 was a randomized placebo controlled trial of D (45mg orally daily) versus P in NSCLC patients previously treated with chemotherapy and an EGFR TKI. The primary outcome was OS. Secondary outcomes included PFS and OS in patients with KRAS wild type (WT) and EGFR mutated (mut) tumors, response rate (RR), toxicity and quality of life.

Results

Patients were randomized 2:1 to D (n = 480), or P (n = 240). Baseline characteristics were well balanced. D improved PFS compared with P (2.7m v 1.4m, HR 0.66, 95%CI 0.55 – 0.79, p < 0.0001), but did not improve OS (6.8m v 6.3m, HR 1.0, 95%CI 0.83-1.21, p = 0.99). Tumor mutation data were available for KRAS in 418 patients and EGFR in 531. Similar proportions of patients allocated to D and P had mutations of KRAS (11.9% v 8.8%) or EGFR (23.8% v 28.3%). The effect of D on OS was similar in EGFR mut (7.2 v 7.5m, HR 0.98, 95%CI 0.67-1.44) and EGFR WT subgroups (6.9 v 5.6m, HR 0.93, 95%CI 0.71-1.21, interaction (int) p = 0.69). However, the effect of D on OS appeared to differ in KRAS WT (7.0 v 5.2m, HR 0.79, 95%CI 0.61-1.03) and KRAS mut subgroups (5.8 v 8.3m, HR 2.10, 95%CI 1.05-4.22, int p = 0.08). RR in KRAS WT was 9.1% v 0.8%, with no responses in KRAS mut. A higher RR was observed with D in EGFR mut (11.4% v 1.5%) than EGFR WT (4.3% v 0%). For PFS, there was a significant interaction between treatment and both EGFR status (HR 0.56 mut v 0.83 WT, int p = 0.049), and KRAS status (HR 1.87 mut v 0.58 WT, int p = 0.011). An exploratory analysis showed this difference was only partly explained by EGFR status (KRAS/EGFR WT HR 0.71 v KRAS WT/EGFR mut HR 0.54). The rate of systemic therapy after disease progression was similar (37% vs 41%).

Conclusions

The effect of D on OS did not differ according to EGFR status. However, there was a trend suggesting a qualitative interaction between D and KRAS status and OS. D was associated with shorter OS in patients with KRAS mut, but longer OS in patients with KRAS WT. These results require validation in future studies.

Disclosure

P.M. Ellis: Peter Ellis received honararia from Pfizer for advisory board meetings in 2011, but not since; F. Perrone: Dr Perrone received honararia from Pfizer for educational activities; A. Morabito: Dr Morabito received honararia from Pfizer for advisory boards; M. Tsao: Ming Tsao has received honararia and research funding from Pfizer; I. Taylor: Ian Taylor is an employee of Pfizer; G. Goss: Glen Goss has received honararia from Pfizer for advisory boards; P.A. Bradbury: Penny Bradbury has no personal disclosures. However, the NCIC CTG received part funding from Pfizer for the conduct of the trial. All other authors have declared no conflicts of interest.