NSCLC patients experience many cancer-related symptoms (sx; e.g. cough, dyspnea, pain, hemoptysis, fatigue). Decreasing tumor burden may reduce/delay these sx and favorably impact global health-related quality of life (HRQOL). Dacomitinib is an irreversible, small molecule inhibitor of EGFR/HER-1, HER-2, and HER-4 tyrosine kinases. In a global multicenter, open-label randomized phase 2 study (NCT00769067) of second/third-line NSCLC, dacomitinib showed improved progression-free survival (PFS; primary objective), hazard ratio 0.66 (95% CI, 0.47, 0.91), two-sided P = 0.012, and manageable toxicity versus erlotinib. Here we report impact on core lung cancer sx .Methods
Patients progressing after one to two prior chemotherapies were randomized 1:1 to dacomitinib (45 mg) versus erlotinib (150 mg) orally QD. A secondary objective was to explore HRQOL. Disease/treatment-related sx were recorded using the EORTC QLQ-C30 and QLQ-LC13 and scored using the scoring manual. Scores were summarized by the mean (and 95% CI) for each group and plotted over time . The mean changes from baseline (Cycle 1, Day 1) were also reported for each group.Results
Between November 2008 and October 2009, 188 patients were randomized. Baseline scores were similar between the two treatments and on-study completion rates were high (>84%). Key NSCLC sx were improved in patients receiving dacomitinib versus erlotinib with clinically meaningful improvements (>10 points on 100 point scale) at specific time points. The difference in mean change from baseline favored dacomitinib for dyspnea, cough, pain and fatigue at most time points over the first 16 weeks (data will be presented). At time points beyond 16 weeks the majority of patients had progressed and sample sizes were too small for meaningful comparison.Conclusions
Dacomitinib demonstrated favorable clinical benefit versus erlotinib and improvements in common NSCLC sx. Such findings are important when considering the totality of benefit of a potential new therapy.Conclusions
1. Ramalingam et al. ESMO 2010; 365PD.Conclusions
2. Fayers et al. EORTC QLQ-C30 scoring manual. EORTC Publications 2001.