Nivolumab, a checkpoint inhibitor, and cabozantinib, a targeted therapy, produced dramatic results when used in combination for patients with newly diagnosed advanced kidney cancer.
Two drugs that doctors now choose from in metastatic kidney cancer when the first treatment fails—the checkpoint inhibitor nivolumab and the targeted therapy cabozantinib—were studied together against the current first-line standard, with dramatic results, according to findings presented this weekend at the European Society for Medical Oncology (ESMO) Virtual 2020 Congress.
Renal cell carcinoma (RCC) is the most common type of kidney cancer and occurs when cancer cells grow in the lining of tiny tubes in the kidney. RCC is associated with hypertension, obesity, and chronic use of OTC pain relievers. When it strikes, RCC can spread quickly to the lungs and vital organs. It accounts for 140,000 deaths worldwide each year and is most common in North America and Europe.
Results of the phase 3 CheckMate 9ER trial, presented Saturday, showed that the nivolumab-cabozantinib combination reduced the risk of death 40% compared with sunitinib, with an HR for overall survival of 0.60 (98.89% CI, 0.40-0.89; P = .010). Progression-free survival, the primary end point, was double compared with sunitinib alone: 16.6 vs 8.3 months (HR, 0.51; 95% CI, 0.41-0.64; P < .0001).
The combination produced a superior objective response rate, 56%, compared with 27% when taking sunitinib; 8% taking the combination achieved a complete response compared with 5% in the sunitinib arm.
According to a statement from ESMO, more than 50% of the patients in the combination arm needed a dose reduction due to adverse events (AEs), but only 3% stopped taking the study regimen compared with 9% who were taking sunitinib. Liver toxicity was more common in the combination arm, although the overall rate of serious AEs was the same.
The study’s lead author, Toni K. Choueiri, MD, of Dana-Farber Cancer Institute and Harvard Medical School, said in the ESMO statement, “The results with combination therapy were statistically significant and clinically meaningful. The risk of progression or death was cut by almost 50%, death was cut by 40%, and the response rate doubled. This will become an important treatment option to choose from.
“The various combination treatments will unlikely be compared head-to-head, but I think quality of life could differentiate this new therapy, as there was a statistical significance favoring the combination arm with both questionnaires we used,” Choueiri said. “Another factor to consider is that clinicians are familiar with both of these drugs.”
Leaders from both Bristol Myers Squibb (BMS), maker of nivolumab (Opdivo), and Exelis, maker of cabozantinib (Cabometyx), said that using the tyrosine kinase inhibitor cabozantinib helps create a tumor environment where the immunotherapy nivolumab is more effective. The regimen seemed to work well for patients regardless of International Metastatic RCC Database Consortium (IMDC) Risk Score.
“We’re encouraged by the significant and consistent efficacy benefits shown in CheckMate 9ER for the first-line treatment of advanced kidney cancer, including all IMDC risk groups and PD-L1 status,” Gisela Schwab, MD, president, Product Development and Medical Affairs, and chief medical officer, Exelixis, said in a statement. “The favorable efficacy and tolerability profile suggests that, if approved, [cabozantinib] in combination with [nivolumab] would be an important new option for patients with advanced kidney cancer.”
“These data are yet another example of the potential of immunotherapy-based combinations to meaningfully extend survival for patients with advanced cancers, strengthening our legacy in the genitourinary space,” said Nick Botwood, MD, vice president, interim head, Oncology Development, BMS.
BMS and Exelixis funded the study.
Choueiri TK. Nivolumab and cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. Presented at: European Society for Medical Oncology Virtual 2020 Congress; September 19-21, 2020. Abstract 696O_PR.