Dr Emmanuel Seront, medical oncologist at Clinique Universitaires Saint-Luc and Dr Marco Gizzi medical oncologist working at the Grand Hôpital de Charleroi and in Clinique Universitaires Saint-Luc, engaged in a discussion regarding the LITESPARK-005 study, which juxtaposed the efficacy of belzutifan against everolimus in patients with extensively treated metastatic clear cell renal cell carcinoma (ccRCC). They regard this study as a pivotal development in clinical practice.
Belzutifan operates as an inhibitor of HIF-2a, a crucial component within the Hypoxia-Inducible Factor (HIF) pathway. The genetic context in many RCC patients entails the loss of Von Hippel-Lindau genes, prompting increased HIF expression. Belzutifan serves to obstruct the heterodimerisation of HIF-2a with HIF-1β and the subsequent activation of oncogenic pathways. This novel oral agent necessitates daily administration at a 120 mg dose and is characterised by a favourable tolerability profile. The principal adverse effects associated with belzutifan are intrinsic to its mode of action, manifesting as anaemia and hypoxia. Notably, these manifestations are generally amenable to effective management, underscoring the necessity of regular patient monitoring.
Crucially, the LITESPARK-005 study presented compelling evidence of a marked enhancement in PFS and ORR compared to everolimus. The data suggest a substantial 25% risk reduction for progression or mortality when employing belzutifan relative to everolimus. Particularly noteworthy is the remarkable sustainability of the treatment response, although data regarding OS await further maturation.
A salient point to consider is that the study’s patient cohort featured individuals who had undergone extensive prior treatment regimens, having received two to three lines of therapeutic interventions, which encompassed immune checkpoint inhibitors and anti-angiogenic agents. Furthermore, subgroup analysis underscores the notion that belzutifan’s therapeutic benefits extend beyond the realm of favourable-risk patients, as it has demonstrated favourable outcomes in cohorts categorised as intermediate and poor prognosis. This observation hints at the potential broad applicability of belzutifan as a promising therapeutic option for an extensive spectrum of ccRCC patients.
References:
Laurence Albiges – Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): Randomized open-label phase III LITESPARK-005 study. ESMO23 – LBA88
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