Camrelizumab and nab-paclitaxel demonstrated promising antitumor activity in immunomodulatory triple-negative metastatic breast cancer (TNBC) patients in FUTURE trial, but the efficacy of adding famitinib to this strategy is under investigation
During ASCO 2021 World Congress, FUTURE-C-PLUS (NCT04129996) was presented, a prospective phase II single-arm trial, evaluating the efficacy and safety of the triple combination of famitinib (a tyrosine-kinase inhibitor targeting VEGFR-2, PDGFR, and c-kit), camrelizumab (an anti-PD-1 antibody), and nab-paclitaxel in patients with immunomodulatory advanced triple-negative breast cancer (TNBC).
Eligible patients were 18 to 70 years of age with unresectable, locally advanced, or metastatic TNBC that was treatment-naive and with immunomodulatory subtype (defined by the presence of CD8+ by immunohistochemistry). Eligible patients received camrelizuma (200mg EV on days 1 and 15 each week) with nab-paclitaxel (100mg/m² EV on days 1, 8 and 15 every four weeks) and famitinib (20mg orally daily). Treatment was continued until disease progression, withdrawal of consent, or limiting toxicity. In the absence of intolerable toxicity, nab-paclitaxel should be administered for a minimum of six cycles. The primary endpoint was the objective response rate according to RECIST v1.1. Predictive biomarkers were explored using targeted sequencing with a panel of 484 genes.
From October 2019 to October 2020, 48 patients were enrolled. Confirmed objective responses were achieved in 39 (81.3%; CI 95% 70.2% – 92.3%) of 48 patients in the intent-to-treat population, and in 39 (84.8%; CI 95% 74.4% – 95.2%) of 46 participants in the population protocol.
The mean response time was 1.8 months. At a mean follow-up of 9.0 months, progression-free survival (PFS) and duration of response data were not mature by the time of analysis. 30 patients (62.5%) are still on treatment in the study. The PFS rate at nine months was 60.2% (95% CI 43.2% – 77.3%).
Grade 3 or 4 adverse events were neutropenia (33.3%), anemia (10.4%), febrile neutropenia (10.4%), thrombocytopenia (8.3%), hypertension (4.2%), hypothyroidism (4.2%), proteinuria (2.1%), septicemia (2.1%) and immuno-mediated myocarditis (2.1%). Adverse events leading to discontinuation of any agent occurred in 6.3% of patients. Two patients had serious adverse events related to treatment. No treatment-related deaths were reported. Biomarker analysis showed that somatic mutations of GSK3A have the potential to predict immunotherapy response.
The researchers conclude that the addition of famitinib to camrelizumab and nab-paclitaxel showed promising antitumor activity as first-line treatment in patients with immunomodulatory TNBC, with a manageable toxicity profile.