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. Academic Article uri icon

Overview

abstract

  • 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 [H0 ]: 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.

authors

  • Reckamp, Karen L
  • Giaccone, Giuseppe
  • Camidge, D Ross
  • Gadgeel, Shirish M
  • Khuri, Fadlo R
  • Engelman, Jeff A
  • Koczywas, Marianna
  • Rajan, Arun
  • Campbell, Alicyn K
  • Gernhardt, Diana
  • Ruiz-Garcia, Ana
  • Letrent, Stephen
  • Liang, Jane
  • Taylor, Ian
  • O'Connell, Joseph P
  • Jänne, Pasi A

publication date

  • February 5, 2014

Research

keywords

  • Adenocarcinoma
  • Carcinoma, Non-Small-Cell Lung
  • ErbB Receptors
  • Lung Neoplasms
  • Quinazolines
  • Quinazolinones

Identity

PubMed Central ID

  • PMC4164026

Scopus Document Identifier

  • 84898023610

Digital Object Identifier (DOI)

  • 10.1002/cncr.28561

PubMed ID

  • 24501009

Additional Document Info

volume

  • 120

issue

  • 8