Cabozantinib May be an Option for Advanced Non-Clear-Cell Renal Cell Carcinoma

Cabozantinib is approved to treat patients with metastatic renal cell carcinoma (RCC) based on studies conducted in those with clear-cell histology, but the activity of this treatment in patients with non-clear-cell RCC is poorly characterized. However, recent real-world research published in The Lancet Oncology supports the anti-tumor activity and safety of cabozantinib in patients with non-clear-cell RCC.

The multicenter, international, retrospective, cohort study included 112 patients with non-clear-cell RCC who were treated at 22 participating centers (21 in the United States and one in Belgium). Eligible patients were those treated with oral cabozantinib during any treatment line between 2015 and 2018. Patients with mixed tumors with a clear-cell histology component were excluded.

The researchers conducted a retrospective chart review to gather demographic, surgical, pathological, and systemic therapy data.

In this cohort, 66 patients (59%) had papillary histology, 17 (15%) had Xp11.2 translocation histology, 15 (13%) had unclassified histology, 10 (9%) had chromophobe histology, and four (4%) had collecting duct histology.

Benefit observed with cabozantinib

Across all histologies, 30 patients (27%) achieved an objective response (95% CI, 19-36), including one complete response and 29 partial responses. Fifty-three patients (47%) had stable disease.

After a median follow-up of 11 months (interquartile range, 6-18 months), the median time to treatment failure was 6.7 months (95% CI, 5.5-8.6), the median progression-free survival was 7 months (95% CI, 5.7-9.0), and the median overall survival was 12 months (95% CI, 9.2-17.0).

At the time of analysis, 38 patients remained on therapy. The median time to treatment failure was 6.7 months. At 6 months, 55% of patients were treatment failure free; at 12 months, 27% of patients were treatment failure free. Overall survival was 79% at 6 months and 51% at 12 months.

The most common any-grade adverse events (AEs) were fatigue (n=58; 52%) and diarrhea (n=38; 34%). The most common grade 3 AEs were skin toxicity (rash and palmar-plantar erythrodysesthesia; n=5; 4%) and hypertension (n=4; 4%). No treatment-related deaths occurred.

Benefits remain across different mutation types

Fifty-four patients had next-generation sequencing data available, and the most frequently altered somatic genes were CDKN2A (n=12; 22%) and MET (n=11; 20%). Response to treatment occurred across different mutation types.