Results of a new study led by Yale Cancer Center (YCC) researchers shows the addition of cetuximab to afatinib versus afatinib alone did not improve outcomes in previously-untreated epidermal growth factor receptor (EGFR) mutant, non-small cell lung cancer (NSCLC). The combination resulted in increased toxicity and more frequent dose-reduction and treatment discontinuation. The findings from the multi-center, randomized SWOG trial are published today online in the Journal of Clinical Oncology (JCO).
“Single-agent EGFR tyrosine kinase inhibitor (TKI) therapy is the standard first-line treatment for patients with EGFR-mutated NSCLC,” said Sarah Goldberg, MD, MPH, Associate Professor Internal Medicine (Medical Oncology) at YCC and lead author of the study. “We aimed to determine whether adding cetuximab to afatinib would improve progression-free survival (PFS) in this treatment setting. In this case, we determined that the addition of the second therapy did not improve outcomes for our patients.”
Patients with EGFR-mutant NSCLC without prior treatment for advanced disease were enrolled in the phase II, multicenter trial and randomized to receive afatinib daily plus cetuximab every two weeks, or afatinib alone. The primary endpoint of the study was PFS. Results showed 174 patients were randomized and 168 (83 on afatinib/cetuximab and 85 on afatinib alone) were eligible to participate. There was no improvement in PFS in patients receiving afatinib plus cetuximab compared to afatinib alone (HR 1.01, 95% CI 0.72-1.43, P = 0.94, median 11.9 months vs 13.4 months). Similarly, there was no difference in response rates (67% vs. 74%, p=0.38) or overall survival (HR 0.82, 95% CI 0.50-1.36, P = 0.44). Toxicity was greater with the combination: grade > 3 adverse events related to treatment occurred in 72% of patients receiving afatinib plus cetuximab compared to 40% of those receiving afatinib alone, most commonly rash and diarrhea. Dose reductions were more common in patients receiving the combination, and 30% of patients in this arm discontinued cetuximab due to toxicity.
“There is currently no role for the combination of afatinib and cetuximab in patients with treatment-naïve EGFR-mutated NSCLC,” said Goldberg. “However further investigation into more tolerable combinations of EGFR TKIs with EGFR antibodies is needed.”