First-line afatinib plus cetuximab for EGFR-mutant non–small cell lung cancer: Results from the randomized phase II IFCT-1503 ACE-lung study

Alexis Benjamin Cortot (1, 2) , Anne Catherine Madroszyk (3, 4) , Étienne Giroux-Leprieur (5, 3, 6) , Olivier Molinier (3, 7) , Élisabeth A. Quoix (3, 8) , Henri Berard (3, 9) , Josiane Otto (3, 10) , Isabelle Rault (3, 11) , Denis L. Moro-Sibilot (3, 12) , Judith Raimbourg (3, 13) , Elodie Amour (3) , Franck Morin (3) , José Hureaux (3, 14, 15) , Lionel Moreau (3, 16) , Didier Debieuvre (3) , Hugues Morel (3, 17) , Aldo Renault (3) , Éric Pichon (3, 18) , Benjamin Huret (3) , Sandrine Charpentier (19) , M. G. Denis (3, 19) , Jacques L. Cadranel (3, 20)

1 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
2 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
3 IFCT - Intergroupe Francophone de Cancérologie Thoracique [Paris]
4 IPC - Institut Paoli-Calmettes
5 BECCOH - Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie
6 Hôpital Ambroise Paré [AP-HP]
7 Centre Hospitalier Le Mans (CH Le Mans)
8 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
9 HIA - Hopital d'instruction des armées Sainte-Anne [Toulon]
10 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
11 CHU Amiens-Picardie
12 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
13 CRLCC René Gauducheau
14 CHU Angers - Centre Hospitalier Universitaire d'Angers
15 UBL - Université Bretagne Loire
16 Hôpitaux Civils de Colmar
17 CHRO - Centre Hospitalier Régional d'Orléans
18 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
19 CHU Nantes - Centre Hospitalier Universitaire de Nantes
20 CHU Tenon [AP-HP]

Purpose: 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 þ cetuximab versus afatinib alone in the first-line treatment of advanced EGFR-mutant NSCLC. Patients and Methods: In this phase II, randomized, open-label study, patients with stage III/IV EGFR-positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib þ cetuximab (group A þ 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 þ 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 þ 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 þ 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 addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR-mutant NSCLC.

Domaines: Cancer

Alexis Benjamin Cortot, Anne Catherine Madroszyk, Étienne Giroux-Leprieur, Olivier Molinier, Élisabeth A. Quoix, et al.. First-line afatinib plus cetuximab for EGFR-mutant non–small cell lung cancer: Results from the randomized phase II IFCT-1503 ACE-lung study. Clinical Cancer Research, 2021, 27 (15), pp.4168-4176. ⟨10.1158/1078-0432.CCR-20-4604⟩. ⟨hal-03401841⟩