Deeper treatment response linked to improved survival in advanced renal cell carcinoma
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CHICAGO — Deeper response to treatment was associated with improved progression-free and overall survival in patients with advanced renal cell carcinoma, according to data from the CheckMate 9ER trial.
“Depth of response, defined as best percent reduction from baseline in sum of diameters of target lesions, has been previously associated with efficacy outcomes of immune checkpoint inhibitor-based regimens and/or targeted therapies in patients with advanced [renal cell carcinoma],” Cristina Suárez, MD, from Vall d’Hebron University Hospital in Spain, said during a presentation of the results at ASCO Annual Meeting.
To evaluate the relationship between depth of response and clinical outcomes, Suárez and colleagues conducted an exploratory post-hoc analysis of the most recent 33-month follow-up data from the phase 3, open-label CheckMate 9ER trial — a study demonstrating improved PFS, OS and objective response rate with nivolumab (Opdivo, Bristol Myers Squibb) plus cabozantinib (Cabometyx, Exelixis) vs. sunitinib malate (Sutent, Pfizer) in patients with untreated advanced renal cell carcinoma (RCC).
For the exploratory analysis, the researchers categorized patients into subgroups based on best overall response and best tumor reduction threshold. These included a complete response subgroup and three subgroups based on partial response with different tumor reduction thresholds — at least 80% (partial response 1), less than 80% but at least 60% (partial response 2) and less than 60% (partial response 3) — and stable and progressive disease subgroups.
PFS and OS were assessed at 6 months after randomization, with PFS including patients who were alive and progression-free and OS including patients who were alive at the 6-month landmark. Other endpoints included time and duration of ORR and treatment-related adverse events within 30 days from the 6-month landmark analysis of OS.
Deeper responses, improved outcomes
At the 6-month landmark, 293 patients within the nivolumab plus cabozantinib arm and 253 patients in the sunitinib arm were alive. Among those who were alive, more patients receiving nivolumab plus cabozantinib had complete response or fell into the partial response 1 or partial response 2 subgroups. When combined, 38% of nivolumab plus cabozantinib group vs. 17% in the sunitinib group had an at least 60% reduction in target lesions. Moreover, only 5% of the nivolumab plus cabozantinib group, as compared with 15% of the sunitnib group, had progressive disease.
Also at the 6-month landmark, deeper responses led to improvements in PFS in both treatment arms, according to Suárez. Notably, the 12-month PFS rates showed increasingly deeper responses led to improved outcomes in PFS, as well as more pronounced improvement observed in the nivolumab plus cabozantinib arm vs. the sunitinib arm.
Deeper responses generally led to improvement in OS as well, with similar OS in the complete response and partial response 1 subgroups in both treatment arms. Additionally, 18-month OS rates by depth of response at the 6-month landmark linked increasingly deeper responses to better OS outcomes, with similar OS rates noted in the complete response and partial response 1 subgroups, Suárez noted.
The researchers also observed numerical improvements in median duration of response with each incremental increase in depth of response in the nivolumab plus cabozantinib arm but not in the sunitinib arm. Furthermore, the median duration of response was not reached in either treatment arm.
In terms of safety, incidence of any-grade or grade 3 or 4 treatment-related adverse events were generally consistent across depth-of-response subgroups, according to Suárez.
General survival benefit
“In this post hoc analysis of the CheckMate 9ER trial, a greater proportion of patients receiving nivolumab plus cabozantinib achieved deeper responses — complete response or partial response 1 or partial response 2 — than those receiving sunitinib, and a lower proportion had progressive disease. And regardless of treatment, deeper responses were generally associated with improved PFS and OS,” Suárez said.
Suárez noted, however, that the analysis was limited by its post-hoc nature, lower number of events and patients in some subgroups, and the fact that it was not powered to detect differences between treatment arms.
“As observed in prior studies of immunotherapy-based treatments, these results suggest that, in general, depth of response may be a useful early indicator of durable efficacy and improved prognosis among patients with untreated advanced RCC receiving nivolumab plus cabozantinib,” Suárez said.
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Suárez C, et al. Abstract 4501. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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