Dr Badami on the Optimal Selection of Second-Line TKIs in ccRCC

“What the participants in the panel discussed was: Would you, in the second-line setting, consider adding a checkpoint inhibitor to a second-line agent? The consensus was no.”

Ami Umesh Badami, MD, medical oncologist, Endeavor Health Medical Group, discusses clinical research that has informed treatment selection in the second-line setting for patients with clear cell renal cell carcinoma (ccRCC).

At an OncLive® State of the Science Summit™ on genitourinary cancer, Badami and colleagues discussed a case study of a patient with metastatic ccRCC who underwent initial nephrectomy followed by active surveillance and a frontline systemic therapy doublet. During the discussion, questions arose regarding optimal hypothetical second-line treatment options for similar cases, including whether current data signified a role for immunotherapy agents in this setting, Badami begins.

The phase 3 CONTACT-03 trial (NCT04338269), which evaluated the addition of the PD-L1 inhibitor atezolizumab (Tecentriq) to cabozantinib (Cabometyx) vs cabozantinib alone in patients with advanced RCC who had previously received an immune checkpoint inhibitor, demonstrated no benefit with the combination. Similarly, the phase 3 TiNivo-2 trial (NCT04987203), which assessed tivozanib (Fotivda) plus the PD-1 inhibitor nivolumab (Opdivo) vs tivozanib alone in patients with previously treated ccRCC, showed no significant advantages with the combination as second- or third-line therapy. The findings from these trials highlight that the addition of a checkpoint inhibitor to second-line ccRCC regimens does not improve outcomes regardless of whether the immunotherapy agent targets PD-1 or PD-L1, Badami explains.

Given these findings, the panel discussion pivoted to the selection of appropriate TKIs or alternative classes of therapy in the second-line setting, Badami says. Belzutifan (Welireg), a HIF-2α inhibitor, has shown activity in patients with ccRCC who have received 1 or more prior lines of therapy, she notes. However, this agent is predominantly used in later-line settings rather than as a second-line therapy, she emphasizes. In the presented case, cabozantinib was selected as the second-line agent, partly due to the lack of data with belzutifan at the time of treatment, she concludes.