ABSTRACT
BACKGROUND: Nivolumab and cabozantinib are currently approved agents in metastatic renal cell carcinoma (mRCC) but there are no data available for patients progressing to both treatments. The aim of this study was to compare active therapeutic options and best supportive care (BSC) after progression to nivolumab and cabozantinib in mRCC. METHODS: In this retrospective study, we selected 50 patients from eight Italian centers. The primary endpoint of the study was the overall survival (OS) of patients on active treatment versus BSC. Secondary endpoints were the progression-free survival (PFS) and objective response rate (ORR). The efficacy of active therapy was also investigated. RESULTS: After progression to both nivolumab and cabozantinib, 57.1% of patients were given active treatment (mainly everolimus and sorafenib) while 42.9% received BSC. The median OS was 13 months (95% CI: 4-NR) in actively treated patients and 3 months (95% CI: 2-4) in BSC patients (p = 0.001). Patients treated with sorafenib had better disease control than those treated with everolimus (stable disease: 71.4% vs. 16.7%, progression disease: 14.3% vs. 58.3%; p = 0.03), with no significant differences in PFS (5 and 3 months, 95% CI: 1-6 vs. 2-5; p = 0.6) and OS (12 and 4 months, 95% CI: 3-NR vs. 2-NR; p = 0.2). CONCLUSION: After treatment with both nivolumab and cabozantinib, the choice of a safe active systemic therapy offered better outcomes than BSC.
Subject(s)
Antineoplastic Agents , Carcinoma, Renal Cell , Kidney Neoplasms , Anilides/therapeutic use , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/pathology , Disease Progression , Everolimus/adverse effects , Humans , Kidney Neoplasms/pathology , Nivolumab/therapeutic use , Pyridines , Retrospective Studies , Sorafenib/therapeutic useABSTRACT
BACKGROUND: Bevacizumab has provided encouraging results in relapsed glioblastoma multiforme (GBM). Pre-clinical and clinical investigations also showed that continuous low-dose temozolomide has some antiangiogenic activity. Based on this evidence, a phase II trial was designed to investigate an oral regimen of sorafenib, an oral multikinase inhibitor, and metronomic temozolomide for relapsed GBM. PATIENTS AND METHODS: Forty-three patients (median age=60.0 years) naive for antiangiogenic agents received 400 mg sorafenib twice daily plus TMZ 40 mg/m(2)/day until disease progression. RESULTS: Toxicity, mostly grade 1-2, was manageable. Grade 3-4 toxicities were hand-foot syndrome (n=4), hypertension (n=2), and fatigue (n=3). Five patients (12%) achieved partial response, 18 (43%) stable disease, 20 (48%) showed progression. The median time-to-progression was 3.2 months, 6-month progression-free survival was 26%, and median overall survival was 7.4 months. CONCLUSION: This combination of sorafenib and temozolomide was feasible and safe, showing some activity in patients with relapsed GBM.