Cabozantinib as possible new first-line therapy in translocation renal cell carcinoma

Cabozantinib may be a reasonable therapeutic option for patients with microphthalmia-associated transcriptional factor (MiT) translocation renal cell carcinoma (TRCC) [1]. This is a welcome development for a cancer that currently lacks a standardised treatment approach under either National Comprehensive Cancer Network (NCCN) guidelines or the European Society for Medical Oncology (ESMO) framework.

MiT-family TRCCs are an aggressive subgroup of RCC (making up only about 1 to 5% of all RCCs), which strongly express cellular mesenchymal-epithelial transition factor (c-MET, a tyrosine kinase receptor). Current first-line therapy for these cancers consists of the use of vascular endothelial growth factor receptor (VEGFR)-directed agents; the progression-free survival (PFS) associated with this approach ranges from 3 to 8.4 months.

Cabozantinib is a tyrosine kinase inhibitor (TKI) that inhibits VEGFR, MET, and AXL (also a tyrosine kinase receptor). Dr Jonathan Thouvenin (Institut de Cancerologie Strasbourg Europe, France) reported results from his team’s international, multicentre, retrospective analysis of 24 patients with MiT-family TRCC who had been treated with cabozantinib at any time. Determined were 3 endpoints: objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors [RECIST], PFS, and overall survival (OS). The median age of the patients was 43.5 years and 17 (70.8%) were female. The majority (17, 70.8%) had undergone previous nephrectomy. The lungs were the most frequent site of metastasis (62.5%), followed by retroperitoneal lymph nodes (45.8%), and bone (37.5%).

Most patients had undergone previous treatment; 16/24 (66.7%) had received monotherapy and 6/24 (25.0%) combination therapy. Specifically, 11 (45.8%) had received monotherapy VEGFR TKIs; 5 (20.8%) had received monotherapy immune checkpoint inhibitors; 4 (16.7%) had been treated with a combination of VEGFR TKIs and immune checkpoint inhibitors; and 2 (8.3%) had been treated with a combination of immune checkpoint inhibitors.

Of the 24 patients, 7 (29.2%) had received cabozantinib as a first-line therapy, 9 (37.5%) had received it as a second-line therapy, and the remaining 8 (33.3%) as a third-line (or beyond) therapy. Only 4 patients (16.7%) achieved an ORR; 1 (4.2%) was deemed complete and 3 (12.5%) were deemed partial. Of the remaining 20 patients, 11 (45.8%) had stable disease, whereas 9 (37.5%) suffered disease progression. Following a median follow-up of 14 months, the median PFS was 8.4 months (95% CI 3.57–11.57). The median OS was 17 months (CI 95% 10.4–NA).

Treatment-related grade 3–4 adverse events were experienced by 9 patients (37.5%). A further 5 (20.8%) experienced treatment-related adverse events to the extent that they decided to discontinue therapy. There were no treatment-related deaths.

These results constitute real-world evidence that cabozantinib provided a more durable response than that seen with other first-line therapies described in the literature for MiT TRCC systemic treatment.

1. Thouvenin J. Efficacy of cabozantinib in advanced MiT family translocation renal cell carcinomas (TRCC). Abstract 274, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.

 

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Posted on 24 March, 20218 February, 2024