Second-Line Cabozantinib Demonstrates Clinical Activity in Metastatic Renal Cell Carcinoma

Cabozantinib, a tyrosine kinase inhibitor (TKI), as a second-line treatment, showed clinically meaningful activity for patients with metastatic renal cell carcinoma, regardless of prior exposure to vascular endothelial growth factor (VEGF) inhibitors, according to a study published in Clinical Genitourinary Cancer.

“There is a lack of data characterizing the outcomes and treatment patterns associated with this agent post current standard of care [first-line immuno-oncology] combination therapy,” Vishal Navani, MBBS, Tom Baker Cancer Centre, Alberta, Canada, and colleagues wrote. “Furthermore, [second-line] regulatory indications for cabozantinib worldwide are limited to patients who had received prior VEGF [inhibitor] treatment, to reflect the inclusion criteria of METEOR.”

In this study, 346 patients were collected from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) between March 2007 and December 2021. All patients had metastatic renal cell carcinoma and received cabozantinib monotherapy as a second-line treatment after being treated with ipilimumab-nivolumab combination (n = 78), immuno-oncology/VEGF inhibitor combinations (n = 46), pazopanib or sunitinib (n = 161), or some other (n = 61) first-line treatment. Of all the patients included, 12.6% were classified as favorable risk according to the IMDC, 62.6% were classified intermediate risk, and 24.8% were classified poor risk. The primary end points of this study were time to treatment failure, and overall survival (OS).

The median OS of second-line carbozantinib was 21.4 (95% confidence interval [CI], 12.1 to not evaluable [NE]) months for patients who received first-line ipilimumab-nivolumab, 15.7 (95% CI, 9.3 to NE) months for patients who received first-line immune-oncology/VEGF inhibitor, 20.7 (95% CI, 15.6 to 35.6) months for patients who received first-line pazopanib or sunitinib, and 14.3 (95% CI, 10.5 to 28.8) months for patients who received some other first-line therapy (P = 0.28). The 1-year OS was 66.6% for first-line ipilimumab-nivolumab, 54.3% for immuno-oncology/VEGFi, 65.6% for pazopanib or sunitinib, and 56.5% for other first-line therapies. When analyzed by type of first-line therapy, there was no statistical difference detected between the times to treatment failure.

Navani et al concluded, “In a large real world dataset, we identified clinically meaningful activity of [second-line cabozantinib] after all evaluated contemporary [first-line] therapies ... This work can give confidence to clinicians that cabozantinib has activity following [first-line] contemporary [immuno-oncology] combination, irrespective of whether a VEGF [inhibitor] is included.”

Source:

Navani V, Wells JC, Boyne DJ, et al. CABOSEQ: The effectiveness of cabozantinib in patients with treatment refractory advanced renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Clin Genitourin Cancer. Published online July 20, 2022. doi:10.1016/j.clgc.2022.07.008