The addition of cetuximab to afatinib did not show a clinical benefit and led to increased toxicity for treatment-naive patients with EGFR-mutant non-small cell lung cancer (NSCLC), according to the results of the phase 2 randomized SWOG S1403 trial in the Journal of Clinical Oncology (ClinicalTrials.gov Identifier: NCT02438722).
A total of 168 enrolled patients were eligible for analysis, which included 83 patients who were randomly assigned treatment with afatinib and cetuximab and 85who received afatinib alone. Trial accrual was halted on April 23, 2018, when an interim analysis revealed “insufficient evidence” to support further accrual.
The trial failed to meet its primary endpoint, showing no improvement in progression-free survival (PFS) for the combination arm compared with the afatinib alone arm (hazard ratio [HR], 1.01; 95% CI, 0.72 -1.43; P =.94). The median PFS was 11.9 months for the combination arm and 13.4 months for the afatinib alone arm.
Similarly, no overall survival (OS) advantage was seen for the combination arm compared with the afatinib alone arm (HR, 0.82; 95% CI, 0.50-1.36; P =.44), with a 2-year OS rate of 67% for the combination arm and 70% for the afatinib alone arm.
The lack of OS and PFS benefit for the combination arm was consistent among subgroups.
In addition, no difference in response rates was seen between the combination arm and the afatinib alone arm (67% vs 74%, respectively; P =.38).
Grade 3 or worse adverse events related to treatment were significantly more common for the combination arm compared with the afatinib alone arm (72% vs 40%; P<0.0001). One patient on the combination arm died, which was deemed related to treatment.
More than double the patients in the combination arm required a dose reduction of afatinib to 30 mg compared with the afatinib alone arm (56.7% v 26.2%, respectively), and toxicity led to 30% of patients in the combination arm stopping cetuximab. Overall, 14% of patients in the combination arm and 11% in the afatinib arm discontinued the trial as a result of adverse events.
“Why this combination, which is active in the resistance setting, failed in the first-line setting is unclear,” the study authors wrote. One potential explanation offered was that many patients in the combination arm discontinued cetuximab, “which could have diluted any biologic benefit that might have been attained with the combination.”
Goldberg SB, Redman MW, Lilenbaum R, et al. Randomized trial of afatinib plus cetuximab versus afatinib alone for first-line treatment of EGFR-mutant non-small-cell lung cancer: Final results from SWOG S1403. J Clin Oncol. Published online October 6, 2020. doi:10.1200/JCO.20.01149