Cabozantinib, a kinase inhibitor, is approved in metastatic renal cell carcinoma on the basis of studies in clear cell histology. Its activity in non–clear cell renal cell carcinoma is poorly defined. In a retrospective cohort study, Nieves Martinez Chanzá, MD, and colleagues reported that cabozantinib showed antitumor activity and a manageable toxicity profile in patients with advanced non–clear cell renal carcinoma.1 The investigators noted that results of ongoing prospective studies are awaited.
Nieves Martinez Chanzá, MD
The retrospective study involved data from patients with metastatic disease treated with cabozantinib during any treatment line at 21 centers in the United States and 1 in Belgium between 2015 and 2018. Mixed tumors with a clear cell histology component were excluded. Among 112 patients identified at the participating centers, 66 (59%) had 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.
Objective response was observed in 30 patients (27%), including 18 (27%) with papillary histology, 5 (29%) with Xp11.2 translocation histology, 2 (13%) with unclassified histology, 3 (30%) with chromophobe histology, and 2 (50%) with collecting duct histology. An additional 53 patients (47%) had stable disease.
“... this real-world study provides evidence supporting the antitumor activity and safety of cabozantinib across non–clear cell renal cell carcinomas.”— Nieves Martinez Chanzá, MD, et al
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At a median follow-up of 11 months, the median time to treatment failure was 6.7 months, median progression-free survival was 7.0 months, and median overall survival was 12.0 months. Among 54 patients with available next-generation sequencing data, the most frequently altered somatic genes were CDKN2A (12 patients, 22%) and MET (11 patients, 20%).
Objective responses were observed irrespective of mutational status. For example, responses were observed in 4 patients (all with papillary histology) with CDKN2A alterations and in 4 of 10 patients with papillary histology and MET alterations.
The most common adverse events of any grade were fatigue (52%), diarrhea (34%), and skin toxicity (31%). The most common grade 3 adverse events were skin toxicity (rash and palmar-plantar erythrodysesthesia; 4%) and hypertension (4%). No treatment-related deaths were observed.
The investigators concluded, “While we await results from prospective studies, this real-world study provides evidence supporting the antitumor activity and safety of cabozantinib across non–clear cell renal cell carcinomas. 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.”
Lauren C. Harshman, MD
Lauren C. Harshman, MD, of the Lank Center for Genitourinary Cancers, Dana-Farber Cancer Institute, is the corresponding author for The Lancet Oncology article. ■
DISCLOSURE: The study authors’ full disclosures can be found at thelancet.com.
1. Martinez Chanzá N, Xie W, Asim-Bilen M, et al: Cabozantinib in advaned non–clear cell renal cell carcinoma: a multicentre, retrospective, cohort study. Lancet Oncol 20:581-590, 2019.