Effectiveness and Safety of Molecular-Targeted Therapy after Nivolumab Plus Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter, Retrospective Cohort Study

SIMPLE SUMMARY: We evaluated the efficacy and safety of molecular-targeted therapies (MTTs) in 29 patients who discontinued the combination therapy of nivolumab plus ipilimumab (NIVO+IPI) for advanced or metastatic renal cell carcinoma as real-world outcomes. Patients receiving MTTs had a median follow-up of 8 months. The objective response rate was 44.8%, and the disease control rate was 72.4%. After NIVO+IPI, the median overall survival was 18 months, and progression-free survival (PFS) was 8 months. Patients with bone metastases had a significantly shorter median PFS when treated with MTTs after NIVO+IPI than those without bone metastases (4 vs. 12 months, p = 0.012). MTTs may be a useful secondary treatment option after the discontinuation of NIVO+IPI. ABSTRACT: This study aimed to evaluate the effectiveness and safety of molecular-targeted therapies (MTTs) after the discontinuation of nivolumab and ipilimumab (NIVO+IPI) combination therapy in patients who had been diagnosed with advanced/metastatic renal cell carcinoma as real-world outcomes. We enrolled patients treated with MTTs following initial therapy with NIVO+IPI at nine institutions in Japan. We evaluated the objective response rate (ORR) as the primary endpoint and disease control rate (DCR), best overall response, and oncological outcomes (overall survival (OS) and progression-free survival (PFS)) as the secondary endpoints. We also evaluated factors predictive of disease progression after the administration of MTTs. Patients were followed up for a median of 8 months. The ORR was 44.8%, and the DCR was 72.4%. The median OS and PFS of MTTs after NIVO+IPI were 18 months and 8 months, respectively. A total of 31% of patients experienced grade 3/4 MTT-related adverse events. The median PFS in patients with bone metastases was significantly shorter than that in those without bone metastases (4 vs. 12 months, p = 0.012). MTTs may be a useful secondary treatment option after the discontinuation of NIVO+IPI.