Home > Oncology > ESMO 2024 > Genitourinary Cancer > More highlights in Renal Cell Carcinoma

More highlights in Renal Cell Carcinoma

Trial
LITESPARK-005, SUNNIFORECAST
Doi
https://doi.org/10.55788/181f901e
The final analysis of the LITESPARK-005 trial demonstrated improved progression-free survival (PFS) and response rates with belzutifan over everolimus in advanced clear cell renal cell carcinoma (RCC) following PD-(L)1 inhibitor and VEGFR TKI therapy, despite no significant overall survival (OS) benefit. Additonally, the SUNNIFORECAST trial showed that dual checkpoint inhibitor therapy (nivolumab/ipilimumab) improved 12-month survival rates in advanced non-clear cell RCC, especially in PD-L1-positive patients, although median OS remained similar between immunotherapy and standard treatments.
Belzutifan is a treatment option in advanced clear cell RCC after PD-(L)1 inhibitor and VEGFR TKI

Previous results from the phase 3 LITESPARK-005 study showed an improved PFS and objective response rate (ORR) with belzutifan over everolimus in patients with advanced clear cell RCC after PD-(L)1 inhibitor and VEGFR TKI therapy [1]. Prof. Brian Rini (Vanderbilt-Ingram Cancer Center, Nashville, TN, USA) now presented results from the final analysis after a median follow-up of 35.8 months [2].

The 12-month PFS rate was 33.7% versus 17.6% in participants treated with belzutifan (n=374) and everolimus (n=372), respectively; the 24-month PFS rate was 17.5% versus 4.1% (HR 0.75; 95% CI 0.63–0.88). However, no OS benefit of belzutifan was observed. Median OS was 21.4 months versus 18.2 months, respectively (HR 0.92; 95% CI 0.77–1.10; P=0.18). Objective response rate favoured belzutifan over everolimus: 22.7% (3.5% complete response; 19.3% partial response) versus 3.5% (0% complete response; 3.5% partial response). In addition, the median duration of response was improved with belzutifan: 19.3 versus 13.7 months. No new safety signals for belzutifan were observed.
Dual checkpoint inhibitor improves survival in advanced/metastatic non-clear cell RCC

Non-clear cell RCC is a rare and heterogeneous disease comprising more than 20 histological and molecular defined entities. The phase 2, investigator-driven SUNNIFORECAST trial (NCT03075423) enrolled 309 therapy-naïve patients with metastatic or locally advanced non-clear cell RCC (nearly 60% papillary RCC, 20% chromophobe RCC). They were randomised 1:1 to first-line double immunotherapy (nivolumab/ipilimumab, 4 cycles) plus nivolumab maintenance therapy versus standard-of-care (predominantly TKI monotherapy). Prof. Lothar Bergmann (University Hospital Frankfurt, Germany) presented the results [3].

OS rate at 12 months, the primary endpoint of SUNNIFORECAST, favoured double immunotherapy: 86.9% versus 76.8% (P=0.0141). However, the median OS was not significantly different between both treatment arms: 42.4 versus 33.9 months, respectively (P=0.292). Participants with PD-L1 ≥1% had a significant OS benefit of double immunotherapy over standard-of-care (HR 0.56; P=0.031) whereas those with PD-L1 <1% had not (HR 1.40; P=0.244). No PFS benefit was observed.

  1. Choueiri TK, et al. N Eng J Med 2024;391:710-721.
  2. Rini B, et al. Final analysis of the phase 3 LITESPARK-005 study of belzutifan versus everolimus in participants with previously treated advanced clear cell renal cell carcinoma. Abstract LBA74, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
  3. Bergmann L, et al. Prospective randomised phase-II trial of ipilimumab/nivolumab versus standard of care in non-clear cell renal cell cancer: Results of the SUNNIFORECAST trial. Abstract LBA75, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

Copyright ©2024 Medicom Medical Publishers



Posted on