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Author Notes:

Corresponding author: Karen L. Reckamp, MD, City of Hope, 1500 East Duarte Road, Duarte, CA 91010; Fax: (626) 930-5461; kreckamp@coh.org

We thank all of the participating patients and their families, as well as the global network of investigators, research nurses, study coordinators, and operations staff.

Medical writing support was provided by Christine Arris at ACUMED (Tytherington, UK) with funding from Pfizer Inc.

Drs. Ruiz‐Garcia, Liang, Taylor, Gernhardt, and O'Connell are employees of Pfizer and own Pfizer stock.

Stephen Letrent and an immediate family member are employees of Pfizer and own Pfizer stock.

Dr. Reckamp received research funding from Pfizer.

Dr. Camidge served Pfizer in an advisory role.

Dr. Engelman received honoraria from Genentech/Roche, and received research funding from Novartis.

He also received remuneration from Pfizer for use of cell lines for which he is a coinventor, and has an EGFR/MET patent that has been licensed by Ventana and owned by Roche (no compensation to date).

Dr. Koczywas received honoraria from Pfizer and Genentech.

Dr. Gadgeel received honoraria from Pfizer.

Alicyn K. Campbell and an immediate family member were previously employed by Pfizer (neither hold current employment with Pfizer).

Dr. Campbell is currently employed by Genentech, a member of the Roche Group.

Dr. Jänne has been a consultant for Boehringer‐Ingelheim, Genentech/Roche, AstraZeneca, and Pfizer.

Drs. Giaccone, Khuri, and Rajan have no conflicts of interest to disclose.


Research Funding:

This study was sponsored by Pfizer Inc.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • adenocarcinoma
  • non-small cell lung cancer
  • nonadenocarcinoma
  • erlotinib
  • dacomitinib
  • PF-00299804
  • EGFR
  • QLQ-C30

A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non-small cell lung cancer after failure of prior chemotherapy and erlotinib

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Journal Title:



Volume 120, Number 8


, Pages 1145-1154

Type of Work:

Article | Final Publisher PDF


BACKGROUND This phase 2 trial (ClinicalTrials.gov identifier NCT00548093) assessed the efficacy, safety, and impact on health-related quality of life of dacomitinib (PF-00299804), an irreversible tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, in patients with KRAS wild-type non-small cell lung cancer (NSCLC). METHODS Patients with advanced NSCLC, progression on 1 or 2 regimens of chemotherapy and erlotinib, KRAS wild-type or known EGFR-sensitizing mutant tumor, and Eastern Cooperative Oncology Group performance status of 0 to 2 received 45 mg of dacomitinib once daily continuously in 21-day cycles. RESULTS A total of 66 patients enrolled (adenocarcinoma, n = 50; those without adenocarcinoma [nonadenocarcinoma], n = 16). The objective response rate (ORR) for patients with adenocarcinoma (primary endpoint) was 5% (2 partial responses; 1-sided P = .372 for null hypothesis [H 0 ]: ORR ≤ 5%) and 6% (1 partial response) for patients with nonadenocarcinoma. Responders included: 2 of 25 EGFR mutation-positive tumors; 1 of 3 EGFR wild-type with HER2 amplification. Median progression-free survival was 12 weeks overall (n = 66) and 18 weeks (n = 26) for patients with EGFR mutation-positive tumors. Common treatment-related adverse events were of grade 1 or 2 severity, manageable with standard supportive care, and included diarrhea (grade 3 [G3] , 12%), acneiform dermatitis (G3, 6%), exfoliative rash (G3, 3%), dry skin (G3, 0%), fatigue (G3, 3%), and stomatitis (G3, 2%). Six patients (9%) discontinued due to treatment-related adverse events. By patient report, NSCLC symptoms of dyspnea, cough, and pain (chest, arm/shoulder) showed improvement first observed after 3 weeks on therapy. CONCLUSIONS Dacomitinib demonstrated preliminary activity and acceptable tolerability in heavily pretreated patients, and may offer benefit in molecularly defined patient subsets.

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© 2014 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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