1243P - Dacomitinib (D) versus erlotinib (E) in 2nd/3rd line NSCLC: Outcome for Asian patients from the ARCHER 1009 global Phase 3 trial

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Tony Mok
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors T.S.K. Mok1, K.J. O'Byrne2, S.S. Ramalingam3, P.A. Janne4, M. Boyer5, J.S. Ahn6, H. Zhang7, J. O'Connell8, I. Taylor9, C. Mather10, L. Paz-Ares11
  • 1Clinical Oncology, The Chinese University of Hong Kong, N.T. - Hong Kong/CN
  • 2Cancer Services, Princess Alexandra Hospital, Brisbane/AU
  • 3Winship Cancer Institute, Emory University Winship Cancer Institute, 30322 - Atlanta/US
  • 4Thoracic Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 5Medical Oncology, Royal Prince Alfred Hospital, Camperdown/AU
  • 6Haematology/oncology, Samsung Medical Centre, Seoul/KR
  • 7Oncology, Pfizer (China) Research and Development Co. Ltd., Shanghai/CN
  • 8Clinical Oncology, Pfizer Inc., 10017 - New York/US
  • 9Translational Oncology, Pfizer Inc, Groton/US
  • 10Oncology Clinical Development & Medical Affairs, Pfizer Inc, Groton/US
  • 11Medical Oncology, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES

Abstract

Aim

Dacomitinib is an irreversible pan-HER kinase inhibitor with activity in advanced NSCLC. In a Phase 2 trial in pt previously treated with chemotherapy, D showed improved PFS compared to E (median PFS 12 .4 weeks vs. 8.3 weeks; HR 0.66, P = 0.0120). A Phase 3 has been completed (Proc ASCO 2014, Abs 8018).

Methods

The ARCHER 1009 trial randomized patients (pt) with locally advanced/metastatic NSCLC following progression with 1 or 2 prior chemotherapy regimens to blinded treatment with D (45 mg PO QD) or E (150 mg PO QD). The primary endpoint was progression-free survival (PFS) per independent review in the co-primary populations [all patients and those with KRAS WT]. Stratification factors were histology, smoking status, ECOG and Asian versus non-Asian/ Indian race.

Results

Of 878 pt enrolled, 174 (20%) were self-designated as Asian.

The PFS per investigator for Asian pt favored D with HR = 0.811 (95% CI: 0.584-1.125, p value, 1-sided = 0.105); median PFS is 3.7 vs 2.8 months in D and E arms respectively. The Response Rate (CR + PR) was 30.3%and 21.2% in D and E respectively with an odds ratio of 1.62 (95% CI: 0.81-3.23). The most common adverse events for D vs E were diarrhea (79.8 vs 65.9%), rash (42.7 vs 42.4%) or dermatitis acneiform (42.7 vs 52.9%) and stomatitis (65.2 vs 41.2 %) and led to discontinuation in 9 pt on D vs 7 on E.

Dacomitinib (n= 89) Erlotinib (n= 85)
Age, median (range) 60.4 (38.0-88.8) 59.1 (40.0-90.0)
ECOG 0-1/ 2 (%) 93.3/6.7 94.1/5.9
Male/ female (%) 67.4/32.6 61.2/38.8
Smoker/ non-Smoker (%) 66.3/33.7 64.7/35.3
KRAS wt/ mu/ unknown(%) 58.4/7.9/33.7 68.2/3.5/28.2
EGFR Activating mutation (exon 19, 21 or 18) 24 (27%) 20 (23.5%)

Conclusions

The ARCHER 1009 trial suggested improvement in efficacy for D relative to E in Asian patients. The number of patients with EGFRmu was similar between arms. Treatment discontinuation for drug toxicity was uncommon. Survival data is not mature.

Disclosure

T. Mok: Ad boards: AZ, Roche, Eli Lilly, Merck Serono, Eisai, BMS, AVEO, Pfizer, Taiho, Boehringer-Ingelheim, Novartis, GSK Biologicals, Clovis Oncology, Amgen, Janssen, BioMarin Pharmaceutical; Board of directors: IASLC; Corporate-sponsored research: AZ; K.J. O'Byrne: Advisory boards: Pfizer; Other substantive relationships (Honoraria): Pfizer; S.S. Ramalingam: Advisory boards: Pfizer, AstraZeneca, Genentech; P.A. Janne: Advisory boards: Boehringer-Ingelheim, AstraZeneca, Genentech, Pfizer, Merrimack Pharmaceuticals, Clovis Oncology, Sanofi, Chugai; Stock ownership: Gatekeeper Pharmaceuticals; Other substantive relationships: LabCorp; M. Boyer: Advisory boards: Merck Sharpe & Dohme; Corporate-sponsored research: Pfizer, Boehringer-Ingelheim, Merck Sharpe & Dohme, Peregrine Pharmaceuticals; H. Zhang: Employment and stock ownership: Pfizer; J. O'Connell: Employment and stock ownership: Pfizer; I. Taylor: Employment and stock ownership: Pfizer; C. Mather: Employment and stock ownership: Pfizer; L. Paz-Ares: Advisory boards: Pfizer, BMS. All other authors have declared no conflicts of interest.