(ChemotherapyAdvisor) – Dacomitinib (PF-00299804) improved core symptoms of non–small-cell lung cancer (NSCLC) — cough, dyspnea, pain, hemoptysis, and fatigue — when compared with erlotinib in patients with advanced disease who had progressed following one or two prior chemotherapy regimens, according to presenters at the 3rd European Lung Cancer Conference, Geneva, Switzerland, April 18–21.
Previously, results of a global multicenter, open-label randomized Phase 2 study had shown that dacomitinib, an irreversible, small molecule inhibitor of EGFR/HER-1, HER-2, and HER-4 tyrosine kinases, improved progression-free survival (HR, 0.66; 2-sided P=0.012), and had manageable toxicity vs. erlotinib. In this study, 188 patients with NSCLC who had disease progression after one or two prior chemotherapies were randomized 1:1 to dacomitinib 45mg or erlotinib 150mg orally once daily between November 2008 and October 2009.
In this analysis, they investigated whether decreasing tumor burden in patients with NSCLC may reduce or delay symptoms and thus have a favorable impact on global Health Related Quality of Life (HRQOL), a secondary objective of the Phase 2 trial. Disease/treatment-related symptoms were recorded using the EORTCQLQ-C30 and QLQ-LC13 and scored using the scoring manual. Scores were summarized by the mean for each group and plotted over time; mean changes from baseline (Cycle 1, Day 1) were also reported.
Baseline scores were similar between the two treatments and on-study completion rates were high (>84%), they reported. Key NSCLC symptoms were improved in patients receiving dacomitinib vs. erlotinib with clinically meaningful improvements (>10 points on a 100-point scale). The difference in mean change from baseline favored dacomitinib at most time points (e.g., days 10 to 14 and at weeks 4, 8, 12, and 16).
At week 16, mean changes from baseline for dacomitinib vs. erlotinib (the higher the positive score, the worse the symptom) were coughing (-19 vs. 0), dyspnea, 3-item (-8 vs. +1), pain in arm or shoulder (-6 vs. 3+), pain in chest (-5, 5+), dyspnea single item (-5, 1+), fatigue (-2, 6+), and pain (4+, 3+).
“Dacomitinib demonstrated favorable clinical benefit vs. erlotinib and improvements in common NSCLC symptoms,” the investigators noted. “Such findings are important when considering the totality of benefit of a potential new therapy.”