First-line treatment with the tyrosine kinase inhibitor (TKI) dacomitinib was associated with better overall survival (OS) than gefitinib among patients with EGFR-mutation–positive non–small-cell lung cancer (EGFR+ NSCLC), according to a final OS analysis from the phase III ARCHER-1050 trial (abstract 9004), presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
Dacomitinib is an investigational second-generation, irreversible EGFR TKI. The ARCHER-1050 trial investigators sought to compare dacomitinib and gefitinib as oral first-line therapies for EGFR mutation–harboring advanced NSCLC.
“ARCHER-1050 is the first randomized phase III study comparing two EGFR TKIs as first-line therapy for EGFR-positive NSCLC that has demonstrated improvement in OS,” said lead study author Tony S. K. Mok, MD, of the Chinese University of Hong Kong. “Dacomitinib was superior to gefitinib in both progression-free survival and OS, with a 41% lower risk of progressive disease or death and a 24% lower risk of death, with an improvement of 7.3 months in median OS.”
“Median OS of patients with dacomitinib followed by a third-generation EGFR TKI was 36.7 months,” he reported.
A total of 225 patients were randomly assigned to gefitinib (250 mg orally, once daily) study group, and 227 patients received 45 mg oral dacomitinib daily. Patients who had CNS metastases or had received prior TKI therapy or prior systemic treatment of their lung cancer were not eligible to participate. Patients were stratified by EGFR mutation type (exon 19 vs exon 21) and race. Study participants were predominantly Asian (75% of the dacomitinib group and 78% of the gefitinib group), Mok noted.
The research team had previously found a progression-free survival (PFS) advantage for dacomitinib vs gefitinib (median PFS, 14.7 vs 9.2 months; P < .0001), Mok reported.
At a median follow-up of 31.3 months, patients in the dacomitinib group had a median OS of 34.1 months, compared with 26.8 months in the gefitinib group (hazard ratio [HR], 0.76; 95% CI, 0.58.99; P = .04).
When data were analyzed for only Asian study participants, the difference between OS in the dacomitinib and the gefitinib groups fell to statistical nonsignificance.
One patient in the dacomitinib group had CNS metastases at the time of disease progression, compared to 11 patients from the gefitinib group.
Safety profiles were distinct between the two groups. Grade 3 or higher adverse events in dacomitinib and gefitinib-group patients included diarrhea (8.8% vs. 0.9%), paronychia (infection adjacent to the fingernail; 7.5% vs 1.3%), dermatitis acneiform (13.7% vs 0), and stomatitis (inflammation of the lips and mouth; 3.5% vs. 0.4%). Grade 3 or higher conjunctivitis and AST elevation occurred in the gefitinib group but not the dacomitinib group.
Dose reductions were made for 66.5% of patients in the dacomitinib group vs 8% in the gefitinib group, Mok said.
Commenting on this study, Apar K. Ganti, MD, MS, from the Division of Oncology-Hematology at the
University of Nebraska Medical Center, Omaha, told Cancer Network, "These results provide yet another option for patients with EGFR-mutated lung cancer, after the recent results of the FLAURA study of osimertinib. It remains to be seen if dacomitinib or osimertinib will be the new preferred option for the management of treatment-naive patients with EGFR-mutated lung adenocarcinoma."