Dacomitinib Shows Activity in First-Line Treatment of Patients With Clinically or Molecularly Selected Advanced NSCLC
In a phase II trial reported in The Lancet Oncology, Jänne et al found that the pan-HER inhibitor dacomitinib was active in first-line treatment of patients with advanced non–small cell lung cancer (NSCLC) with EGFR mutations or clinical characteristics associated with response to EGFR inhibitors. Dacomitinib has been shown to be active in patients previously treated with gefitinib (Iressa) or erlotinib.
Study Details
The study included 89 patients who were never-smokers (< 100 cigarettes per lifetime) or former light smokers (< 10 pack-years per lifetime) with ≥ 15 years since quitting or who had EGFR mutation regardless of smoking status; 53 patients (60%) had confirmed EGFR mutation, with 45 (85%) having an activating mutation in exon 19 (47%) or exon 21 (38%). Patients received dacomitinib 45 mg or 30 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or patient withdrawal. Approximately 30% of the first 35 patients required modification of the 45-mg dose; patents were subsequently started at 30 mg with the option of increasing the dose to 45 mg at 8 weeks.
Outcomes
Progression-free survival at 4 months, the primary endpoint, was 76.8% (95% confidence interval [CI] = 66.4%–84.4%) in the total population and 95.5% (95% CI = 83.2%–98.9%) among the 45 patients with activating EGFR mutations.
Among all patients, median progression-free survival was 11.5 months, objective response rate was 53.9%, median duration of response was 12.9 months, and estimated median overall survival was 29.5 months. Among the patients with activating mutations, median progression-free survival was 18.2 months, response rate was 75.6%, median duration of response was 17.2 months, and estimated median overall survival was 40.2 months. Outcomes were similar in patients with exon 19 mutations and in those with exon 21 mutations.
Toxicity
The most common treatment-related adverse events of any grade were diarrhea (93%), acneiform dermatitis (78%), dry skin (44%), and stomatitis (40%). The most common treatment-related grade 3 adverse events were acneiform dermatitis (18%), diarrhea (15%), lymphopenia (13%), and hypokalemia (7%); 2 patients (2%) had grade 4 treatment-related events (hypokalemia and dyspnea). Adverse events led to discontinuation of treatment in 14% of patients (6% due to treatment-related events), dose reduction in 32%, and treatment interruption in 56%.
The investigators concluded: “Dacomitinib had encouraging clinical activity as initial systemic treatment in clinically or molecularly selected patients with advanced non-small-cell lung cancer.”
Pasi A. Jänne, MD, of Dana-Farber Cancer Institute, is the corresponding author for The Lancet Oncology article.
The study was funded by Pfizer. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
