97O - EGFR mutant subset analysis from ARCHER 1009: A randomized double blind phase 3 efficacy and safety study of dacomitinib versus erlotinib for the tr...

Date 17 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Luis Paz-Ares
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors L. Paz-Ares1, K. O'Byrne2, T.S.K. Mok3, M. Boyer4, P.A. Jänne5, Z. Goldberg6, C. Mather6, I. Taylor6, H. Zhang6, S.S. Ramalingam7
  • 1Oral And Maxillofacial Surgery, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 2Medical Oncology, Princess Alexandra Hospital, 4102 - Brisbane/AU
  • 3Department Of Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, N/A - Hong Kong/HK
  • 4Chemotherapy Unit, Chris O'Brien Lifehouse, 2050 - Sydney/AU
  • 5Medical Oncology, Dana-Farber Cancer Institute, 02115-5450 - Boston/US
  • 6Oncology, Pfizer Oncology, New York/US
  • 7Medical Oncology, Winship Cancer Institute, Atlanta/US



Introduction: To date there has been no randomized comparisons of EGFR tyrosine kinase inhibitors (TKI) in EGFR mutant NSCLC. Dacomitinib is a potent, irreversible EGFR inhibitor that demonstrated robust activity in a phase 2 study for patients with common activating EGFR mutations. Additionally, preclinical data suggests greater activity in patients with common EGFR activating mutations in exon 19 or 21.

Objectives: ARCHER 1009 (NCT01360554) compared the clinical activity of dacomitinib (D) versus erlotinib (E) in advanced NSCLC.


Patients (pts) with locally advanced/metastatic NSCLC were randomized following progression with 1 or 2 prior chemotherapy regimens to treatment with dacomitinib (D) (45 mg PO QD) or erlotinib (E) (150 mg PO QD) with placebo control for both arms. Archived tumor tissue, ECOG performance status (PS) of 0-2, adequate organ function and informed consent were required. Overall results of this study were previously reported. An analysis was performed among patients with common EGFR activating mutations to compare efficacy of D versus E.


91 (47 on D) pts had EGFR mutations; 76 (37 on D) pts had activating mutations in exon 19 or 21. Independent review for all EGFR mutants at a 56% PFS event rate shows a median PFS of 11.1 months (95% CI 5.6–21.9) for D and 10.0 months (95% CI 7.4–16.6) for E and an unstratified HR of 0.935 (95% CI 0.539-1.624) with 1-sided p= 0.403. Among patients with common activating mutations, 54% achieved a PFS event, the median PFS by independent review of 14.6 months (95% CI 7.4–NR) for D and 9.6 months (95% CI 7.3–16.6) for E and an unstratified HR of 0.707 (95% CI 0.380–1.315) with 1-sided p = 0.136.


This subset analysis from a Phase 3 trial is the only blinded, independently reviewed, direct comparison of EGFR TKIs and suggests potential for improvement in PFS for treatment with D versus E in NSCLC patients with common EGFR activating mutations. This observation will be further evaluated in the ARCHER 1050 study (NCT01774721).

Clinical trial identification NCT01360554


L. Paz-Ares: Received honoraria for scientific advisory board meetings from Roche and Pfizer.

K. O'Byrne: Received honorarium from Pfizer for serving on advisory board meetings and presentations at symposia.

T.S.K. Mok: Received honoraria for serving on advisory board meetings for Astra Zeneca, Boehringer Ingelheim, Roche, Pfizer, Eli Lilly, Novartis, Clovis, Amgen, Janssen, Biomarin, Merck Serono, Bristol Myer Squibb, Aveo, Eisai, and Taiho Pharmaceticals.

M. Boyer: Received honoraria from Boehringer Ingelheim and Eli Lilly. MB has also received travel support from Eli Lilly.

P.A. Jänne: Received honoraria for serving as a consultant for Pfizer, Astra Zeneca, Boehringer Ingelheim, Clovis Oncology, Genentech, Merrimack, Lab Corp, stock ownership in Gatekeeper Pharmaceuticals and receives royalty form a patent licensed to Lab Corp.

Z. Goldberg, C. Mather and H. Zhang: Employee of Pfizer Oncology.

I. Taylor: Employee of Pfizer Oncology and owns stock options in Pfizer Oncology.

S.S. Ramalingam: Received honoraria for serving on advisory board meetings for Amgen, Astra Zeneca, Ariad, Aveo, Boehringer Ingelheim, Celgene, Clovis Oncology, Novartis, Eli Lilly and Genentech.