First-line Afatinib plus Cetuximab for EGFR-mutant Non-small-cell Lung Cancer: Results from the Randomized Phase 2 IFCT-1503 ACE-Lung Study
Mené sur 59 et 58 patients atteints d'un cancer du poumon non à petites cellules de stade avancé et présentant une mutation EGFR, cet essai de phase II évalue l'efficacité, du point de vue du délai avant échec du traitement, et la toxicité de l'ajout du cétuximab à l'afatinib
Résumé en anglais
Purpose:Double inhibition of 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 efficacy and toxicity of afatinib+cetuximab versus afatinib, in first-line treatment of advanced EGFR-mutant NSCLC.
Experimental Design:In this phase 2, non-comparative, randomized, open-label study, patients with stage III/IV EGFR-positive NSCLC were randomly assigned (1:1) to receive afatinib (A) or afatinib+cetuximab (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 EGFR circulating tumor DNA in plasma was performed.
Results: 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. The percentage of patients without treatment failure at 9 months was similar (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 PFS and OS, showed no improvement with the combination. There was a slight numerical increase in grade {greater than or equal to}3 adverse events in group A+C . Allele frequency of the EGFR gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received.
Conclusions: These results suggest that adding cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR-mutant NSCLC.
