Nivolumab + cabozantinib combo maintains survival benefit, response in advanced RCC

The combination therapy of nivolumab plus cabozantinib (NIVO + CABO) continues to show long-term survival benefits and response rates over sunitinib at 55 months in patients with previously untreated advanced renal cell carcinoma (RCC), according to updated results of the CheckMate 9ER study presented at ASCO GU 2024.

In the primary analysis, NIVO + CABO demonstrated superiority over sunitinib in terms of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR), and health-related quality of life (HRQoL) over sunitinib, and these benefits have been sustained for an extended period of 55 months, said lead author Dr Maria Bourlon from the Urologic Oncology Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, Mexico.

The study included 651 participants with previously untreated advanced RCC who were randomized to receive NIVO 240 mg IV Q2W + CABO 40 mg QD (n=323) or sunitinib 50 mg QD for 4 weeks on each 6-week cycle (n=328).

Over a median follow-up of 55.6 months, NIVO + CABO led to longer median PFS (16.4 vs 8.4 months; hazard ratio [HR], 0.58) and OS (46.5 vs 36.0 months; HR, 0.77) relative to sunitinib. [ASCO GU 2024, abstract 362]

ORR was higher with NIVO + CABO vs sunitinib (55.7 percent vs 27.7 percent), as were complete response (13.6 percent vs 4.6 percent) and partial response (42.1 percent vs 23.2 percent).

The benefits of NIVO + CABO over sunitinib were generally consistent across subgroups, including International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) status and baseline organ sites of metastases.

In in the IMDC intermediate/poor-risk subgroup (IMDC prognostic risks score 1 or 2/3–6), patients on NIVO + CABO had longer median PFS (15.4 vs 7.1 months; HR, 0.56) and OS (43.9 vs 29.3 months; HR, 0.73), as well as higher ORR (52.6 percent vs 23.0 percent) than those on sunitinib.

As for the IMDC favourable-risk cohort, the NIVO + CABO arm had better PFS and ORR than the sunitinib arm (median 21.4 vs 12.8 months; HR, 0.69 [PFS] and 66.2 percent vs 44.4 percent [ORR]). However, the median OS did not differ between treatment arms (52.9 vs 58.9 months; HR, 1.10).

Grade ≥3 adverse events (AEs) occurred in 68 percent of patients on the combo regimen compared with 55 percent of those in the sunitinib arm, with 28 percent vs 11 percent, respectively, leading to treatment discontinuation.

The most common AEs observed with the combo regimen were hypertension, palmar-plantar erythrodysesthesia, and diarrhoea.

The safety profile was consistent with previous reports, and no new safety concerns were observed, Bourlon noted.

In an exploratory HRQoL analysis, NIVO + CABO recipients in the ITT cohort had significantly better HRQoL than those on sunitinib, as measured by the FKSI*-19 total score (difference, 2.04; p=0.0009) as well as the EQ-5D-3L VAS** score (difference, 3.91; p=0.0003), compared with sunitinib.

A similar trend was observed in the IMDC intermediate/poor-risk population, but no between-group differences were seen in the favourable-risk cohort, said Bourlon.

“With improved treatment options, more patients are surviving substantially longer, and many receive treatment for an extended period. Therefore, overall efficacy, safety, and QoL benefits as well as individual patient characteristics are important considerations when selecting appropriate therapy,” said the researchers. [N Engl J Med 2021;384:829-841]

Overall, the findings show that “NIVO + CABO continues to maintain meaningful long-term benefits over sunitinib in terms of PFS, OS, and ORR rates,” said Bourlon. “These extended follow-up results support NIVO + CABO as a standard of care for previously untreated advanced RCC.”