Famitinib with camrelizumab and nab-paclitaxel for advanced immunomodulatory triple-negative breast cancer (FUTURE-C-PLUS): an open-label, single-arm, phase 2 trial
Mené sur 48 patientes atteintes d'un cancer du sein triple négatif de stade avancé (durée médiane de suivi : 17 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse, et la toxicité d'un traitement combinant famitinib (un inhibiteur de tyrosine kinase ciblant VEGFR2, PDGFR et c-kit), camrélizumab et nab-paclitaxel
Purpose: Camrelizumab, a monoclonal antibody against PD-1, plus nab-paclitaxel exhibited promising antitumor activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC). Famitinib is a tyrosine kinase inhibitor targeting VEGFR2, PDGFR and c-kit. We aimed to assess the efficacy and safety of a novel combination of famitinib, camrelizumab and nab-paclitaxel in advanced immunomodulatory TNBC. Patients and Methods: This open-label, single-arm, phase II study enrolled patients with previously untreated, advanced, immunomodulatory TNBC (CD8 immunohistochemical staining {greater than or equal to} 10%). Eligible patients received 20 mg of oral famitinib on days 1-28, 200 mg of intravenous camrelizumab on days 1 and 15, and intravenous nab-paclitaxel 100 mg/m2 on days 1, 8 and 15 in 4-week cycles. The primary endpoint was objective response rate (ORR), as assessed by investigators per RECIST v1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety and exploratory biomarkers. Results: Forty-eight patients were enrolled and treated. Median follow-up was 17.0 months (range, 8.7-24.3). Confirmed ORR was 81.3% (95% CI, 70.2-92.3), with 5 complete and 34 partial responses. Median PFS was 13.6 months (95% CI, 8.4-18.8), and median DOR was 14.9 months (95% CI, NE-NE). Median OS was not reached. No treatment-related deaths were reported. Among 30 patients with immunohistochemistry, 13 (43.3%) were PD-L1-positive, and PD-L1 was associated with favorable response. PKD1 and KAT6A somatic mutations were associated with therapy response. Conclusions: The triplet regimen was efficacious and well tolerated in previously untreated, advanced, immunomodulatoryTNBC. The randomized controlled FUTURE-SUPER trial is underway to validate our findings.