Details

Autor(en) / Beteiligte

• Lee, Chung-Han
• Voss, Martin H
• Carlo, Maria Isabel
• Chen, Ying-Bei
• Zucker, Mark
• Knezevic, Andrea
• Lefkowitz, Robert A
• Shapnik, Natalie
• Dadoun, Chloe
• Reznik, Ed
• Shah, Neil J
• Owens, Colette Ngozi
• McHugh, Deaglan Joseph
• Aggen, David Henry
• Laccetti, Andrew Leonard
• Kotecha, Ritesh
• Feldman, Darren R
• Motzer, Robert J

Titel

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates

Ist Teil von

• Journal of clinical oncology, 2022-07, Vol.40 (21), p.2333-2341

Ort / Verlag

United States: Wolters Kluwer Health

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• To assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non-clear-cell renal cell carcinoma (RCC). Patients had advanced non-clear-cell renal carcinoma who underwent 0-1 prior systemic therapies excluding prior immune checkpoint inhibitors. Patients received cabozantinib 40 mg once daily plus nivolumab 240 mg once every 2 weeks or 480 mg once every 4 weeks. Cohort 1 enrolled patients with papillary, unclassified, or translocation-associated RCC; cohort 2 enrolled patients with chromophobe RCC. The primary end point was objective response rate (ORR) by RECIST 1.1; secondary end points included progression-free survival, overall survival, and safety. Next-generation sequencing results were correlated with response. A total of 47 patients were treated with a median follow-up of 13.1 months. Objective response rate for cohort 1 (n = 40) was 47.5% (95% CI, 31.5 to 63.9), with median progression-free survival of 12.5 months (95% CI, 6.3 to 16.4) and median overall survival of 28 months (95% CI, 16.3 to not evaluable). In cohort 2 (n = 7), no responses were observed; one patient had stable disease > 1 year. Grade 3/4 treatment-related adverse events were observed in 32% treated patients. Cabozantinib and nivolumab were discontinued because of toxicity in 13% and 17% of patients, respectively. Common mutations included and in cohort 1 and and in cohort 2. Objective responses were seen in 10/12 patients with either or mutations. Cabozantinib plus nivolumab showed promising efficacy in most non-clear-cell RCC variants tested in this trial, particularly those with prominent papillary features, whereas treatment effects were limited in chromophobe RCC. Genomic findings in non-clear-cell RCC variants warrant further study as predictors of response.