Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: a randomized, double-blind, phase 2 trial – REACHIN
Mené sur 66 patients atteints d’une tumeur des voies biliaires de stade localement avancé ou métastatique, cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression, du régorafénib après l’échec d’une chimiothérapie de première ligne à base de gemcitabine et de sels de platine (durée médiane de suivi : 24 mois)
Résumé en anglais
Background : There is a high unmet clinical need for treatments for advanced/metastatic biliary tract cancers (BTC) after progression on first-line chemotherapy. Regorafenib has demonstrated efficacy in some gastrointestinal tumors that progress on standard therapies. Patients and Methods : REACHIN was a multicenter, double-blind, placebo-controlled, randomized phase 2 study designed to evaluate the safety and efficacy of regorafenib in patients with nonresectable/metastatic BTC that progressed after gemcitabine/platinum chemotherapy. Patients were randomly assigned 1:1 to best supportive care plus either regorafenib 160 mg once daily 3 weeks on/one week off or placebo until progression or unacceptable toxicity. No crossover was allowed. The primary objective was progression-free survival (PFS). Secondary objectives were response rate, overall survival (OS), and translational analysis. Results : Sixty-six patients with intra-hepatic (n=42), peri-hilar (n=6), or extra-hepatic (n=9) cholangiocarcinoma, or gallbladder carcinoma (n=9) were randomized, 33 to each treatment group. At a median follow-up of 24 months, all patients had progressed and 6 patients were alive. Median treatment duration was 11.0 weeks (95%CI: 6.0-15.9) in the regorafenib group and 6.3 weeks (95%CI: 3.9-7.0) in the placebo group (p=0.002). Fourteen of 33 patients (42%) in the regorafenib group had a dose reduction. Stable disease rates were 74% (95%CI: 59-90) in the regorafenib group and 34% with placebo (95%CI: 18-51; p=0.002). Median PFS in the regorafenib group was 3.0 months (95%CI: 2.3-4.9) and 1.5 months (95%CI: 1.2-2.0) in the placebo group (hazard ratio 0.49; 95%CI: 0.29-0.81; p=0.004) and median OS was 5.3 months (95%CI: 2.7-10.5) and 5.1 months (95% CI: 3.0-6.4), respectively (p=0.28). There were no unexpected/new safety signals. Conclusion : Regorafenib significantly improved PFS and tumor control in patients with previously treated metastatic/unresectable BTC in the second- or third-line setting.
