Highlights on renal cancer

Professor Emmanuel Seront, medical oncologist at Cliniques Universitaires Saint-Luc in Belgium, provides an overview of key developments in renal cancer presented at ASCO GU 2024.

The initial groundbreaking study, CheckMate-67T, scrutinizes the efficacy and feasibility of biweekly IV administration versus the four-weekly SC administration of nivolumab in metastatic RCC patients. This phase 3 non-inferiority trial focuses on PK and efficacy as endpoints. Significantly, the trial meets its endpoints, demonstrating similar drug distribution after IV or SC administration, and comparable ORR and PFS. Safety profiles are consistent between both arms, suggesting the potential for more patient-friendly administration of checkpoint inhibitors with equivalent outcomes.

The second trial addresses the overexpression of CA IX in clear cell RCC, indicative of disease aggressiveness and progression. Using radioligand imaging with a peptide targeting CA IX radiolabeled with gallium-68, the trial aims to identify and treat patients. Despite its small scale, the technique provides exceptional images with minimal clinical toxicity.

At ASCO GU 2024, an update on various trials was presented, including CheckMate-214, a well-established randomized phase 3 trial comparing NIVO+IPI versus SUN in first-line metastatic RCC. Positive results on primary endpoints OS, PFS, and ORR are reported at intermediate analysis. An eight-year follow-up reveals sustained effects in intermediate and poor-risk groups for NIVO+IPI, with a 30% reduction in the risk of death. However, in favourable risk groups, SUN demonstrates superior PFS and ORR, with similar overall survival. Notably, NIVO+IPI shows a lower ORR but achieves durable responses, including a higher complete response compared to SUN.

LITESPARK-005, comparing belzutifan to everolimus, now includes patient-related outcomes. Importantly, QoL is superior with belzutifan compared to advanced clear cell RCC patients who received prior immune checkpoint and anti-angiogenic treatments, making a compelling case for belzutifan treatment.

KEYNOTE-B61, a phase 2 trial evaluating pembrolizumab with lenvatinib for non-clear cell RCC, addresses an urgent unmet medical need. The combination yields a 50% ORR and an approximately 80% disease control rate. Notably, the regimen exhibits a 50% response rate, with half of the patients experiencing durable responses exceeding 18 months. While more patients need inclusion for robust analysis, the results are promising.

KEYNOTE-564 is a phase 3 randomized trial evaluating adjuvant pembrolizumab for one year versus placebo in resected clear cell RCC patients with intermediate/high risk of recurrence. Positive preliminary results in DFS demonstrate a 32% risk reduction. Ongoing analyses reveal that pembrolizumab decreases the risk of death by 38% in the ITT population. Notably, at two years, there is a 5% absolute benefit in survival across all subgroups, marking a significant advancement with consideration for potential adverse effects.

References:

George S et al, 2024, Subcutaneous Nivolumab Versus Intravenous Nivolumab in Patients With Previously Treated Advanced or Metastatic Clear Cell Renal Cell Carcinoma: Pharmacokinetics, Efficacy, and Safety Results From CheckMate 67T. J Clin Oncol 42, S4; LBA360

Hofman MS et al, 2024, First-in-human safety, imaging and dosimetry of [68Ga]Ga-DPI-4452, a novel CA IX-targeting peptide, in patients with clear cell renal cell carcinoma. J Clin Oncol 42, S4; LBA373

Tannir N et al, 2024, Nivolumab plus Ipilimumab vs Sunitinib for First-Line Treatment of Advanced RCC: Long-Term Follow-up Data from the Phase 3 CheckMate 214 Trial. J Clin Oncol 42, S4; LBA363

Powles T et al, 2024, Belzutifan Versus Everolimus in Participants With Previously Treated Advanced Renal Cell Carcinoma: Patient-Reported Outcomes in the Phase 3 LITESPARK-005 Study. J Clin Oncol 42, S4; LBA361

Voss M et al, 2024, First-line Pembrolizumab plus Lenvatinib for Non–clear Cell RCC: Extended Follow-up of the Phase 2 KEYNOTE-B61 Study. J Clin Oncol 42, S4; LBA2

Choueiri  T et al, 2024, Overall Survival Results from the Phase 3 KEYNOTE-564 Study of Adjuvant Pembrolizumab vs Placebo for the Treatment of Clear Cell RCC. J Clin Oncol 42, S4; abstr LBA359

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