Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer : a multicenter, randomized phase IIb study
Mené sur 192 patients atteints d'un cancer du pancréas de stade localement avancé, cet essai multicentrique de phase IIB évalue, du point de vue de la survie globale à 1 an, l'intérêt d'ajouter le nimotuzumab à la gemcitabine, en fonction de la présence de mutations du gène KRAS
Background : This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-EGFR monoclonal antibody, compared to gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. Patients and Methods : Patients (pts) with previously untreated, unresectable, locally-advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary endpoint was overall survival (OS), secondary endpoints included time to progression, overall response rate (ORR), safety and quality of life (QoL). Results : A total of 192 pts were randomised, with 186 of them being evaluable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared to 19%/10% for gem plus placebo (HR = 0.69; p = 0.03/HR=0.68; p = 0.02). Median OS/PFS was 8.6/5.1 months (mo) for gem plus nimo versus (vs) 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; p = 0.0341/HR=0.68; p = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 vs 5.6 mo, p = 0.03) Conclusion : This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially those patients with KRAS wildtype seem to benefit. The study was registered as protocol ID OSAG101-PCS07, NCT00561990, and EudraCT 2007-000338-38.