Dr Gopal on the Evolution of TKI/IO Combination Approaches in RCC

Nikhil A. Gopal, MD, assistant professor, urology, assistant professor, College of Medicine - Memphis, Department of Urology, The University of Tennessee Health Science Center, discusses the transition of the use of single-TKIs to TKI/immuno-oncology (IO) combinations in the treatment of patients with renal cell carcinoma (RCC).

In recent years, TKI/IO treatment combinations have become a standard of care in the frontline setting for patients with RCC, with the notable exception being the IO/IO combination of nivolumab (Opdivo) and ipilimumab (Yervoy), Gopal begins. He goes on to emphasize that it is notable how immunotherapy has evolved from being scarcely discussed in 2014 and 2015, to now having 5 agents approved for frontline use. The challenge now lies in determining the most suitable combination for each patient, Gopal adds, saying that in his perspective, the combination of TKIs and IO therapies appears to yield higher objective response rates (ORRs).

For example, the TKI/IO combinations of pembrolizumab (Keytruda) plus axitinib (Inlyta) and lenvatinib (Lenvima) plus pembrolizumab elicited higher ORRs in clinical trials that supported their FDA approvals compared with nivolumab plus ipilimumab, which was approved based on data from the phase 3 CheckMate 214 trial (NCT02231749), he continues. Therefore, for patients with significant disease burden and concerns about disease progression leading to critical complications such as impending cord compression or debilitating bone pains hindering mobility could benefit a TKI/IO combination over nivolumab and ipilimumab, Gopal elucidates.

Although it is challenging to directly compare results across different trials, real-world decision-making often necessitates such comparisons to provide patients with actionable insights, Gopal expands. On the other hand, nivolumab and ipilimumab offer the advantage of the longest follow-up time, with data extending up to 8 years, he says Interestingly, and with this extended follow-up, the overall survival curves continue to demonstrate a benefit compared with sunitinib (Sutent) alone, Gopal concludes.