Welireg Outperforms Afinitor in Advanced Clear Cell Kidney Cancer

Patients with preterated advanced clear cell renal cell carcinoma (ccRCC), tended to see better outcomes with Welireg (belzutifan) than Afinitor (everolimus), according to interim findings from the phase 3 LIFESPARK-005 trial presented at the 2023 European Society of Medical Oncology Annual Congress.

The trial included 746 adult patients with ccRCC who were treated with one to three prior regimens, including a checkpoint inhibitor and VEGF-TKI. Participants were randomly assigned to receive Welireg (374 patients) or Afinitor (372 patients) until disease progression or unacceptable toxicity.

Primary endpoints were progression-free survival (PFS; time from treatment until disease worsening or death) and overall survival (OS; time from treatment until death of any cause). Second endpoints were objective response rate (ORR; percentage of patients whose disease shrinks or disappears from treatment), safety, and time to deterioration (TTD).

Findings showed that at a median follow-up of 18.4 months, PFS and ORR were better in the Welireg arm compared to the Afinitor. ORR was 21.9% for the Welireg arm, compared with 3.5% in the Afinitor arm, with Welireg ORR increasing over time to reach 22.7%.

There was no statistical significance in OS between the two arms, at 21 versus 17.2 months, respectively.

“(Welireg) demonstrated a significant improvement in PFS. … Similar findings were noted at the second interim analysis,” study author Dr. Laurence Albiges, medical oncologist and head of the Department of Oncology at Gustave Roussy in Paris, said in a presentation of the findings.

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At a later follow-up at 25.7 months, PFS and ORR data were consistent with those observed in the initial analysis. Complete responses (CR) occurred in 13 (3.5%) of patients in the Welireg arm, compared with 0 patients in the Afinitor arm.

Further, the 12-month PFS rates were 33.7% in the Welireg arm, compared with 17.6% in the Afinitor arm, while 18-month PFS rates were 22.5% and 9%, respectively.

“With regard to subgroup analysis, all subgroups favored (Welireg),” Albiges explained. “(I’d like to) stress the fact that (Welireg) demonstrated activity in both intermediate- and poor-risk (International Metastatic RCC Database Consortium) categories.”

A total of 22.6% and 5% of patients in the (Welireg) and (Afinitor) arms were continuing treatment at the time of data collection, while 5.9% and 14.7%, respectively, stopped therapy due to any side effects. Grade 3-5 (moderate to fatal) side effects occurred in 38.7% of patients in the Welireg arm, compared with 39.4% in the Afinitor arm.

TTD per the functional assessment for cancer therapy protocol was better for those in the Welireg arm (median not reached) compared with 12 months for those in the Afinitor arm.

“Ultimately, LIFESPARK-005 is the first positive phase 3 (trial) in patients with advanced RCC who had failed immune checkpoint [inhibitors] and VEGF TKIs,” Albiges said.

A final analysis of LIFESPARK-005 will be presented at a future medical meeting.

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