Data from First-Line Afatinib plus Cetuximab for <i>EGFR</i>-Mutant Non–Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study

Abstract

&lt;div&gt;AbstractPurpose:&lt;p&gt;Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non–small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced &lt;i&gt;EGFR&lt;/i&gt;-mutant NSCLC.&lt;/p&gt;Patients and Methods:&lt;p&gt;In this phase II, randomized, open-label study, patients with stage III/IV &lt;i&gt;EGFR&lt;/i&gt;-positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C). Oral afatinib 40 mg was given once daily; 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 primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of &lt;i&gt;EGFR&lt;/i&gt; circulating tumor DNA in plasma was performed.&lt;/p&gt;Results:&lt;p&gt;Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A + C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A + C), and median TTF was 11.1 (95% CI, 8.5–14.1) and 12.9 (9.2–14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A + C. Allele frequency of the &lt;i&gt;EGFR&lt;/i&gt; gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received.&lt;/p&gt;Conclusions:&lt;p&gt;These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced &lt;i&gt;EGFR&lt;/i&gt;-mutant NSCLC.&lt;/p&gt;&lt;/div&gt;