Treatment with the second-generation EGFR tyrosine kinase inhibitor (TKI) dacomitinib resulted in improved overall survival (OS) over gefitinib in treatment-naive patients with non–small-cell lung cancer (NSCLC) and activating EGFR mutations, according to a randomized phase III trial.
The first generation of EGFR TKIs including gefitinib and erlotinib showed clear advantages in terms of response rate, progression-free survival (PFS), and quality of life over chemotherapy. “However, none of these studies were able to demonstrate an improvement in OS, nor was a significant improvement in OS observed in a randomized, direct comparison of gefitinib and erlotinib,” wrote study authors led by Yi-Long Wu, MD, of the Guangdong Academy of Medical Sciences in China.
So far, no studies of the second generation of these agents have demonstrated an OS benefit over the first generation. The ARCHER 1050 trial previously reported a significant improvement with dacomitinib over gefitinib in terms of PFS; the new analysis includes the OS data for a total of 452 patients with newly diagnosed NSCLC and activating EGFR mutations.
The patient characteristics were generally well balanced between the dacomitinib (227 patients) and gefitinib (225 patients) arms, though there were more men in the gefitinib arm (44% vs 35.7%). The results, from an interim analysis, included a follow-up of 31.1 months; the results were published in the Journal of Clinical Oncology.
The median OS was 34.1 months with dacomitinib, compared with 26.8 months with gefitinib, for a hazard ratio of 0.760 (95% CI, 0.582–0.993; P = .0438). At 30 months, the OS rate was 56.2% with dacomitinib and 46.3% with gefitinib. Brain metastases were the site of progression for 1 dacomitinib patient and for 11 gefitinib patients.
Though the study wasn’t powered for subgroup analyses, preliminary results showed broadly similar OS outcomes across subgroups, including those with specific EGFR mutations and others.
Following discontinuation of study treatment, 49.8% of dacomitinib patients and 62.2% of gefitinib patients went on to receive a subsequent therapy. Chemotherapy was given to 27.8% of dacomitinib patients and 35.6% of gefitinib patients, while third-generation EGFR TKIs were used in approximately 10% of each group.
“Dacomitinib is the first EGFR TKI to show a significant improvement in OS in a randomized, head-to-head comparison with another EGFR TKI for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR activating mutations,” the authors wrote. “Dacomitinib should be considered one of the standard treatment options for this population.”