The second-generation EGFR tyrosine kinase inhibitor (TKI) dacomitinib significantly improved progression-free survival over gefitinib as a first-line therapy for EGFR mutation–positive non–small-cell lung cancer (NSCLC), according to a randomized phase III trial.
First-generation EGFR TKIs including gefitinib and erlotinib are reversible inhibitors that selectively target EGFR; the newer generation of agents, including dacomitinib and afatinib, are irreversible and have activity against EGFR/HER1, HER2, and HER4.
“The advantages of second-generation EGFR TKIs as first-line therapy for patients with EGFR-positive NSCLC have been clearly shown against chemotherapy but, when studied head-to-head against a first-generation TKI, the benefits were unclear,” wrote study authors led by Yi-Long Wu, MD, of the Guangdong Academy of Medical Sciences in Guangzhou, China.
The new ARCHER 1050 trial was an international, multi-center, phase III study that randomized 452 patients with newly diagnosed NSCLC and one EGFR mutation. Patients received either dacomitinib (227 patients) or gefitinib (225 patients), and the median follow-up period was 22.1 months. Results were published online ahead of print in Lancet Oncology.
Patients were well matched between the groups. Most patients were never-smokers (65% in dacomitinib group, 64% in gefitinib group), and most had stage IV disease at screening (81% in both groups).
At the end of the follow-up period, 60% of dacomitinib and 80% of gefitinib patients had progressed. The median progression-free survival was 14.7 months with dacomitinib compared with 9.2 months with gefitinib, for a hazard ratio for progression of 0.59 (95% CI, 0.47–0.74; P < .0001). At 24 months, the progression-free survival rates were 30.6% with dacomitinib and 9.6% with gefitinib.
Response rates were similar between the groups, but duration of response was longer with the study drug than with gefitinib. Based on investigator assessment, those who responded in the dacomitinib group had a duration of response of 15.9 months, compared with 9.2 months with gefitinib (P < .0001).
Overall survival data was not yet mature, with 33% of dacomitinib patients and 40% of gefitinib patients having died at the time of data cut-off.
Several grade 3/4 adverse events occurred more frequently with dacomitinib than with gefitinib. These included dermatitis acneiform (14% with dacomitinib vs none with gefitinib) and diarrhea (8% vs 1%). Raised alanine aminotransferase levels were more common with gefitinib, occurring in 8% compared with 1% of dacomitinib patients. More dacomitinib patients required a dose reduction.
“Dacomitinib treatment was superior to gefitinib with respect to progression-free survival and duration of response in the first-line treatment of patients with EGFR-mutation positive NSCLC and should be considered as a new treatment option for this population,” the authors concluded.