Dr. Kumar on the Future of Triplet Regimens in Metastatic RCC

Rohit Kumar, MD, assistant professor of Medicine, University of Louisville, medical oncologist, University of Louisville Health, Brown Cancer Center, discusses the current and future uses of triplet combinations in metastatic renal cell carcinoma (RCC).

Immuno-oncology (IO)–based doublet combinations with other IO agents or TKIs have become the standard of care in the frontline setting for patients with metastatic RCC, and these combinations include ipilimumab (Yervoy) plus nivolumab (Opdivo) or nivolumab plus cabozantinib (Cabometyx).

TKI and IO combinations have been established across clinical trials, and NCCN guidelines currently recommend axitinib (Inlyta) plus pembrolizumab (Keytruda), cabozantinib plus nivolumab, and Lenvatinib (Lenvima) plus pembrolizumab, Kumar explains.

Although these doublet combinations have an established role in the treatment of RCC, triplet combinations could represent the next logical step for investigators, Kumar notes. Specifically, Kuman ponders if an IO-IO combination could become a triplet with the addition of a TKI.

For example, the phase 3 COSMIC-313 trial (NCT03937219) examined the combination of cabozantinib with nivolumab and ipilimumab, and the study met meet its primary end point of progression-free survival (PFS). Additionally, the ongoing phase 3 PDIGREE study (NCT03793166) is examining different ways of combining and sequencing cabozantinib plus ipilimumab and nivolumab.

Although COSMIC-313 had a PFS positive outcome, it is vital to be vigilant for overall survival data the further determine the possible benefit, along with any additional adverse effects (AEs) associated with the triplet, Kumar says. A key for investigators will be to weigh the risk of safety vs the survival benefits, Kumar says.

Although there was a PFS benefit in COSMIC-313, the response rates for the triplet also left something to be desired, Kumar says, adding that the results were similar to what is seen with just an immunotherapy-based doublets. Triplet therapy remains potential way to improve the treatment landscape in RCC; however, more research is still needed, Kumar concludes.