Cetuximab plus afatinib combo of no benefit in advanced EGFR-mutant NSCLC

Use of cetuximab in combination with afatinib for the first-line treatment of patients with advanced nonsmall cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutation does not appear to improve outcomes as compared with afatinib alone, according to the results of a phase II trial.

The trial randomized 117 patients with stage III/IV EGFR-positive NSCLC to receive afatinib alone (n=59) or in combination with cetuximab (n=58). Afatinib 40 mg was given orally once daily, whereas cetuximab 250 mg/m² was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m² for 6 months.

The study was terminated prematurely due to futility. Specifically, there was no difference in the percentage of patients without treatment failure at 9 months (59.3 percent with monotherapy vs 64.9 percent with combination). The median time to treatment failure (TTF) was 11.1 (95 percent confidence interval [CI], 8.5–14.1) and 12.9 (9.2–14.5) months, respectively.

Results for other outcomes, including progression-free survival (PFS) and overall survival, were the same, with the combination showing no significant advantage over afatinib monotherapy.

There was a slight increase in grade ≥3 adverse events in the combination group.

Finally, patients with allele frequency of the EGFR gene mutation in circulating tumour DNA at baseline had shorter PFS, regardless of the treatment received.

The results do not warrant further investigation of the combination of cetuximab and afatinib in treatment-naïve advanced EGFR-mutant NSCLC.