Cabozantinib plus nivolumab effective in advanced non-clear cell RCC
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Key takeaways:
- Updated phase 2 data showed promising efficacy of cabozantinib plus nivolumab in patients with papillary, unclassified or translocation-associated RCC.
- The safety profile was similar to what was previously reported for this combination.
CHICAGO – Cabozantinib plus nivolumab showed promising efficacy in patients with papillary, unclassified or translocation-associated renal cell carcinoma, according to updated phase 2 study results presented at ASCO Annual Meeting.
“The combination of cabozantinib with nivolumab is approved for use in treating advanced or metastatic clear cell renal cell carcinoma, based on the results of the CheckMate 9ER trial,” Kelly N. Fitzgerald, MD, of Memorial Sloan Kettering Cancer Center, said in the presentation. “However, prior to this study, the combination has not been prospectively evaluated in patients with nonclear cell renal cell carcinoma.”
Researchers performed this extended follow-up from a clinical trial reported in 2021 on a cohort of patients with papillary, unclassified or translocation-associated RCC. They also included patients with chromophobe RCC, but this was closed early for lack of efficacy.
Patients received cabozantinib (Cabometyx, Exelixis) 40 mg by mouth daily plus nivolumab (Opdivo, Bristol Myers Squibb) 240 mg IV every 2weeks, with an option to switch to 480 mg IV every 4weeks after the third cycle.
The primary endpoint was ORR (evaluated by RECIST) and the secondary endpoints included PFS, OS, duration of response and safety. Researchers also conducted correlative analyses by next generation sequencing.
Overall, 40 advanced non-clear cell RCC patients received treatment with a median follow-up time of 34 months. Of these, 26 patients were previously untreated and 14 received one prior treatment line (10 had prior VEGF-targeted therapy and eight had prior mTOR-targeted therapy). In total, 80% of patients had papillary histology, 15% had unclassified histology without papillary features and 5% had translocation-associated RCC, according to Fitzgerald.
The researchers found an ORR of 48% (95% CI, 31.5–63.9).
“Because of the small sample size, there was really no strong correlation between the specific disease histologies and response,” Fitzgerald said. “Amongst patients with papillary RCC, there was one primary progression event and one patient achieved a complete response.”
For secondary endpoints, median PFS was 13 months (95% CI: 7, 16), with a PFS of 51% (95% CI: 34, 65) at 12 months and 23% (95% CI: 11, 37) at 24 months. In total, 27 deaths occurred in the patient cohort, according to Fitzgerald. Median OS was 28 months (95% CI: 23, 43), with an OS of 70% (95% CI: 53, 82) at 18 months and 44% (95% CI: 28, 60) at 36 months. PFS and OS were similar for previously treated and untreated patients. Median duration of response was 17 months (95% CI: 10, 36) for patients who responded.
“The safety profile was similar to what has been already reported for the combination,” Fitzgerald said in the presentation.
Overall, 88% of patients experienced adverse effects of any grade and 55% experienced grade 3/4 adverse events. The researchers also reported grade three or four AST or ALT elevations in 18% and 23% of patients. Study therapy was discontinued in 28% of patents due to toxicity, according to the abstract.
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