LITESPARK-005 update: Belzutifan benefits East Asians with advanced RCC

Treatment with belzutifan improves progression-free survival (PFS) and objective response rate (ORR) in East Asian patients with advanced clear-cell renal cell carcinoma (RCC) compared with everolimus, according to the updated subgroup data of the phase III LITESPARK-005 trial presented at ESMO Asia 2024.

At a median follow-up of 33.4 months, belzutifan treatment led to a longer PFS (median 7.5 vs 5.7 months; hazard ratio [HR], 0.54) and a higher 24-month PFS rate (30 percent vs 4 percent) than treatment with everolimus. [ESMO Asia 2024, abstract LBA2]

In addition, patients receiving belzutifan had an ORR of 30.8 percent; none in the everolimus group had an ORR. The estimated difference between arms was 28.8 percent.

“Taken together, with a >2-year minimum follow-up, PFS and ORR continued to favour belzutifan over everolimus,” said Dr Jae Lyun Lee from Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

This subgroup analysis included 78 East Asian patients enrolled from Korea, Taiwan, Thailand, and Japan with advanced clear-cell RCC who had disease progression after treatment with an anti-PD-(L)1 inhibitor and a VEGF-TKI. Participants were randomized in a 1:1 ratio to receive either oral belzutifan 120 mg/day (median age 60 years, 85 percent male) or everolimus 10 mg/day (median age 67 years, 74 percent male) until unacceptable toxicity, disease progression, or investigator or patient decision to withdraw.

At data cutoff, the median overall survival (OS) was 29.7 months in the belzutifan group and 30.8 months in the everolimus group. A comparison between arms yielded an HR of 0.76, but the difference did not reach statistical significance.

Belzutifan treatment resulted in a higher 24-month OS rate compared with everolimus treatment (59 percent vs 56 percent).

In terms of safety, the rate of grade 3–5 treatment-related adverse events (AEs) was higher in the belzutifan vs the everolimus arm (53 percent vs 33 percent), but there were fewer serious AEs with the former (16 percent vs 26 percent).

One death occurred in the belzutifan group.

The most common all-cause AE observed with belzutifan was anaemia (84 percent); with everolimus, the most common was stomatitis (46 percent).

Of note, the safety profile observed in the East Asian subset was consistent with that previously observed in the intention-to-treat (ITT) population. No new safety signals were observed with belzutifan, said Lee.