Results from a recent study suggest that the antitumor activity of cabozantinib is not limited to patients with clear-cell renal cell carcinoma (RCC) and that the drug provides significant clinical benefit to certain patients with non-clear-cell histology (Lancet Oncol. 2019 Feb 28. Epub ahead of print).

“The activity of cabozantinib in patients with non-clear-cell renal cell carcinoma is poorly characterized,” said Nieves Martínez Chanzá, MD, Dana-Farber Cancer Institute,

Harvard Medical School, Boston, Massachusetts, and colleagues, who sought to evaluate the antitumour activity and toxicity of the drug in this patient population.

The retrospective cohort study by Dr Chanzá and colleagues included 112 patients with metastatic non-clear-cell RCC who received cabozantinib therapy at 1 of 22 centers across the United States and Belgium between 2015 and 2018. Patients with mixed tumors with a clear-cell histology component were excluded from the study.

Investigators at each institution used uniform templates to ensure consistent gathering of demographic, surgical, pathological, and systemic therapy data. The main end points of the study were the estimated number of patients who achieved an objective response, time to treatment failure, and overall survival (OS) posttreatment.

Among the patients included in the study, 66 (59%) had non-clear-cell RCC with papillary histology, 17 (15%) had Xp11.2 translocation histology, 15 (13%) had unclassified histology, 10 (9%) had chromophobe histology, and 4 (4%) had collecting duct histology.

Overall, 30 (27%, 95% confidence interval [CI], 19-36) patients achieved an objective response across all histologies. At a median follow-up of 11 months, findings demonstrated a median time to treatment failure of 6.7 months (95% CI, 5.5-8.6), median progression-free survival of 7.0 months (95% CI, 5.7-9.0), and median OS of 12.0 months (95% CI, 9.2-17.0).

Fatigue and diarrhea were the most frequently reported adverse events of any grade (52% and 34%, respectively). The most common grade 3 adverse events were skin toxicity (4%) and hypertension (4%), and there were no treatment-related deaths.

Among the 54 patients who had next-generation sequencing data available, the most frequently altered somatic genes were CDKN2A (22%) and MET (20%), with responses seen regardless of mutational status.

“[T]his real-world study provides evidence supporting the antitumour activity and safety of cabozantinib across non-clear-cell [RCCs],” Dr Chanzá and colleagues said.

“Continued support of international collaborations and prospective ongoing studies targeting non-clear-cell renal cell carcinoma subtypes and specific molecular alterations are warranted to improve outcomes across these rare diseases with few evidence-based treatment options,” they concluded.—Hina Khaliq