A140 plus mFOLFOX6 compared with cetuximab plus mFOLFOX6 for first-line RAS wild-type metastatic colorectal cancer: A randomized clinical trial
Mené sur 688 patients atteints d'un cancer colorectal de stade métastatique sans mutation RAS (durée médiane de suivi : 19,6 mois), cet essai randomisé de phase III évalue l'efficacité, du point de vue du taux de réponse objective, de l'ajout de A140 (un anticorps anti-EGFR) ou de cétuximab à une chimiothérapie de première ligne de type mFOLFOX6
Purpose: EGFR inhibition, combined with chemotherapy, forms a mainstay of treatment of first-line RAS wild-type (RASwt) metastatic CRC (mCRC). We compared the anti-EGFR antibody, A140, with cetuximab (both combined with chemotherapy) for RASwt mCRC.
Methods: In this phase 3, randomized, double-blind, multi-center equivalence trial in China, patients were randomized (1:1) to oxaliplatin, 5-fluorouracil, and leucovorin (modified [m] FOLFOX6), plus either A140 or cetuximab for ≤16 weeks until disease progression or unacceptable toxicity. After the 16-week treatment period, patients who investigators deemed could benefit received A140 plus mFOLFOX6. Eligible patients were 18-75 years old with histologically confirmed RASwt mCRC and an ECOG score of 0-1. Primary endpoint was objective response rate (ORR [RECIST v1.1]), per independent review committee, over the 16 weeks. A140 was considered equivalent if the 90% CIs for the ORR ratio were between 0.83-1.20. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, immunogenicity, and pharmacokinetics.
Results: Overall, 688 patients were randomized to A140 (n=341) or cetuximab (n=347). As of 22-Mar-2023, the ORR was 71.0% (A140) and 77.5% (cetuximab); the ORR ratio was 0.93 (90% CI, 0.87-0.99). With a median follow-up of 19.6 months, no notable differences in PFS, OS, or duration of response were observed between arms. Safety profiles and immunogenicity were similar between arms and no new safety signals were observed.
Conclusion: A140 plus mFOLFOX6 is equivalent to cetuximab plus mFOLFOX6 for RASwt mCRC, with no appreciable differences in safety profiles. A140 plus mFOLFOX6 may provide a new treatment option for patients with RASwt mCRC.
European Journal of Cancer , résumé, 2025