1228O - Dacomitinib (PF-00299804), an irreversible pan-her tyrosine kinase inhibitor (TKI), for first-line treatment of EGFR-mutant or HER2-mutant or -ampli...

Date 30 September 2012
Event ESMO Congress 2012
Session NSCLC, metastatic I
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Pasi Janne
Authors M. Kris1, Z. Goldberg2, P.A. Janne3, D. Kim4, R. Martins5, T.S.K. Mok6, J. O'Connell7, S.I. Ou8, I. Taylor9, H. Zhang10
  • 1Thoracic Oncology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 2Oncology, Pfizer, San Diego/US
  • 3Thoracic Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 4Department Of Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 5Thoracic/head And Neck Oncology, Ùniversity of Washington/Seattle Cancer care Alliance, Seattle/US
  • 6Department Of Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, CN- - Shatin, Hong Kong/CN
  • 7Oncology, Pfizer, New York/US
  • 8Chao Family Comprehensive Cancer Center, University Of California Irvine Medical Center, University of California, Irvine, Orange/US
  • 9Translational Oncology, Pfizer Inc, Groton/US
  • 10Oncology, Pfizer (China) Research and Development Co. Ltd., Shanghai/CN

Abstract

Background

Dacomitinib irreversibly inhibits EGFR, HER2 and HER4, and showed superior activity vs. reversible EGFR TKI in EGFR-mutant lung cancer models, including resistant forms. This open-label Phase II study evaluates dacomitinib in patients with EGFR-mutant or HER2-amplified or -mutant advanced NSCLCs.

Methods

Patients had stage IIIB/IV adenocarcinoma, no prior systemic treatment (EGFR cohort), had smoked <10 pack years (none within 15 years of enrolment) or had known EGFR mutation. Patients with HER2 amplifications or mutations, could have had any number of prior lines of therapy. Patients received dacomitinib orally once daily continuously at 45 mg, or 30 mg with the option to escalate to 45 mg; evaluation was every 28 days. Endpoints included progression-free survival rate at 4 months (PFS@4M, primary); PFS, partial response (PR) rate; and safety.

Results

89 patients were enrolled and dosed in the EGFR cohort; 46 had EGFR mutation in exons 19 (n = 25) or 21 (n = 21) and 32 (70%) were female. 34/46 evaluable patients with EGFR exon 19 or 21 mutations had a PR (PR rate = 74%; 95% CI: 59–86; exon 19 = 72%; exon 21 = 76%). Preliminary PFS were similar for exons 19 and 21. Preliminary PFS@4M was 96% (95% CI: 84–99), preliminary PFS rate at 12 months was 74% (95% CI: 59–85) and preliminary median PFS was 17 months (95% CI: 13–24). Median duration of tx was 14 months. To date, 17 patients have been dosed in the HER2 cohort (3 with amplification). For 16 patients with response data, there are 2 PR (1 confirmed), both with HER2 mutation. 5 patients had SD as their best response. Common side effects included dermatitis acneiform (grade 3/4 = 16.9%/0) and diarrhea (13.5%/0). 5 patients in total discontinued treatment due to drug-related toxicity.

Conclusions

74% of patients with EGFR exon 19 or 21 mutant lung cancers experienced PRs with 1st-line dacomitinib; preliminary PFS rate was 74% at 1 year; preliminary median PFS was 17 months; PR rates and preliminary PFS were similar for patients with EGFR exon 19 and 21 mutations; further research is planned in these patient populations. There are early signs of activity of dacomtinib in targeting HER2 in advanced NSCLCs and recruitment continues.

Disclosure

M. Kris: Advisory relationship with Pfizer, Boehringer Ingelheim, Genentech/Roche (compensated). Research funding from Pfizer, Boehringer and Ingelheim.

Z. Goldberg: Employed by Pfizer as a Medical Director. Holds Pfizer stock.

P.A. Janne: Advisory / consultant relationship with Boehringer Ingelheim, Roche, Genentech, Abbott, Astra-Zeneca, Pfizer, Sanofi and Teva (compensated). Other renumeration from LabCorp (compensated).

D. Kim: Advisory relationship with Pfizer (compensated). Received honoraria from Pfizer.

R. Martins: Research funding from Pfizer.

T.S.K. Mok: Advisory relationship with Astra Zeneca, Roche, Eli Lilly, Merck Sorono, Eisai, BMS, BeiGene, AVEO, Pfizer, Taiho, Boehringer Ingelheim, GSK Biologicals (compensated). Received honoraria from all the above. Research funding from AstraZeneca.

J. O'Connell: Employed by Pfizer as Senior Director. Holds Pfizer stock.

S. Ou: Advisory relationship with Pfizer and Genentech (compensated). Honoraria from Pfizer, Genentech and Eli Lilly. Research funding from Pfizer.

I. Taylor: Employed by Pfizer as a Senior Director. Holds Pfizer stock.

H. Zhang: Employed by Pfizer as a Senior Manager. Holds Pfizer stock.