Dr Xu on Treatment Sequencing Considerations in Metastatic Renal Cell Carcinoma

Wenxin (Vincent) Xu, MD, physician, Dana-Farber Cancer Institute, and assistant professor of medicine, Harvard Medical School, discusses the factors he takes into account when sequencing treatment options for patients with metastatic renal cell carcinoma (RCC).

Every patient is unique and comes with their own set of considerations, with a key difference between patients being the severity of treatment-related toxicities in the frontline setting, Xu begins. In the second line, some patients who were initially treated with an immunotherapy plus TKI regimen may be worn down by TKI toxicity, Xu continues. For these patients, belzutifan (Welireg) is an option, allowing the patient to take a break from the rigors of TKI toxicity, Xu says.

In the phase 3 LITESPARK-005 trial (NCT04195750), patients with previously treated, advanced RCC who received belzutifan experienced a prolonged time to deterioration (TTD) by FKSI-DRS, QLQ-C30 GHS/QoL, and QLQ-C30 PF scores compared with those who were treated with the kinase inhibitor everolimus (Afinitor). At a median follow-up of 25.7 months (range, 16.8-39.1), the median TTD was not reached vs 11.99 months with belzutifan and everolimus, respectively, by FKSI-DRS (HR, 0.53; 95% CI, 0.41-0.69; P < .0001), 19.35 months vs 10.19 months, respectively, by QLQ-C30 GHS/QoL (HR, 0.75; 95% CI, 0.58-0.96; P = .019), and 19.32 months vs 13.83 months, respectively, by QLQ-C30 PF (HR, 0.93; 95% CI, 0.72-1.20; P = .55).

Conversely, patients who can tolerate TKI toxicities can receive a TKI in the second or even third line, Xu says. Options in later lines include cabozantinib (Cabometyx) or lenvatinib (Lenvima) plus everolimus; these regimens are still highly active in this setting, Xu explains. The goal is to sequence treatments in a manner that gives patients the best chance at a great response without compromising their safety or quality of life, Xu concludes.