Nivolumab–cabozantinib ‘a potential first-line option’ for advanced RCC
medwireNews: The phase 3 CheckMate 9ER trial has demonstrated significantly improved outcomes with the combination of nivolumab and cabozantinib versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (RCC).
The primary endpoint of progression-free survival (PFS) and the secondary endpoints of overall survival (OS) and objective response rate (ORR) were significantly better with the combination, “while maintaining significantly better quality of life over time versus sunitinib,” said Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) at the ESMO Virtual Congress 2020.
“These results support nivolumab plus cabozantinib as a potential first-line option for patients with advanced renal cell carcinoma,” he added.
After a median follow-up of 18.1 months, PFS as assessed by blinded independent central review was a median of 16.6 months for the 323 participants who were randomly assigned to receive the PD-1 inhibitor nivolumab 240 mg every 2 weeks alongside the multitargeted tyrosine kinase inhibitor (TKI) cabozantinib at a daily dose of 40 mg.
This was significantly longer than the median of 8.3 months achieved by their 328 counterparts who received sunitinib 50 mg/day on a 4 weeks on, 2 weeks off schedule, and equated to a significant 49% reduction in the risk for progression or death with the combination.
OS was similarly improved with nivolumab plus cabozantinib versus sunitinib; the median was unreached in both groups at the time of analysis, but the combination was associated with a significant 40% reduction in the risk for death.
Additionally, the ORR was significantly higher among combination- than sunitinib-treated patients, at 55.7% and 27.1%, respectively, and the median duration of response was longer, at 20.2 versus 11.5 months.
The efficacy benefits afforded by nivolumab–cabozantinib were consistently maintained across predefined subgroups, including those defined by IMDC risk status, tumor PD-L1 expression, and bone metastases, commented Choueiri.
More than half (56.3%) of patients in the combination arm required a dose reduction of cabozantinib (nivolumab dose reductions were not permitted), but only 15.3% discontinued one or both drugs due to treatment-related adverse events (TRAEs) and just 3.1% discontinued both drugs.
In the sunitinib group, the proportion of patients who required a dose reduction was 51.6% and the rate of discontinuation due to TRAEs was 8.8%.
The presenter highlighted that “quality of life was maintained over time with [the combination] compared with a consistent deterioration from baseline with sunitinib,” as indicated by the total score of the FKSI-19 patient-reported questionnaire.
Patients in the combination arm also reported improvements relative to baseline in the disease-related symptom subscale, whereas those in the sunitinib arm experienced declines from week 7 onwards, with the between-group differences reaching statistical significance at “almost all timepoints,” reported Choueiri.
Noting that immunotherapy-based combinations are the first-line standard of care in advanced RCC, discussant Camillo Porta (University of Bari Aldo Moro, Italy) wondered how best to choose between the options, given that “direct comparisons between studies which are extremely different” are fraught with problems.
He suggested that “the only possible, though highly empiric, driver of our therapeutical choice should be the biological aggressiveness of the tumor,” with the combination of an immune checkpoint inhibitor and a VEGFR–TKI being used for “very aggressive disease” and an immunotherapy combination used otherwise.
The discussant also highlighted open questions worthy of investigation, such as using VEGFR–TKIs for a limited period at the start of combination therapy and “exploring different schedules of the available combinations.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group