Belzutifan improves PFS, ORR in clear cell renal cell carcinoma

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Published: 22 Oct 2023
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Dr Toni Choueiri - Dana-Farber Cancer Institute, Boston, USA

Dr Toni Choueiri speaks to ecancer about the phase 3 LITESPARK-005 study comparing belzutifan with everolimus in pretreated advanced clear cell renal cell carcinoma, data from which he presented at ESMO 2023.

Belzutifan is an oral inhibitor that targets HIF-2α. It is approved in the US for patients with VHL disease-associated RCC, pNET, and CNS haemangioblastoma.

During his presentation, Dr Choueiri highlighted that belzutifan had a statistically significant improvement in PFS and ORR compared to everolimus for patients with advanced ccRCC after immune checkpoint and anti-angiogenic therapies.

Furthermore, the safety profile of belzutifan was consistent with prior reports, and no new safety signals were observed.

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Belzutifan improves PFS, ORR in clear cell renal cell carcinoma

Dr Toni Choueiri - Dana-Farber Cancer Institute, Boston, USA

We have seen at ESMO ’23 really some intriguing results from LITESPARK-005. We were all waiting for that study, that is a pivotal study of the HIF2 inhibitor single agent belzutifan versus everolimus in patients whose tumour progressed on prior PD-1 inhibitor and prior VEGF TKI. Heavily pre-treated patients, a significant proportion of patients had three prior lines of therapy so they were going as a fourth line on the study. Over 700 patients were randomised to everolimus, an mTOR inhibitor, against post-VEGF, post-PD-1, versus belzutifan.

Progression free survival, one of the primary endpoints, was significant – 25% decrease in the risk of progression or death, a hazard ratio of 0.75. OS was not significant, despite the hazard ratio less than 1.0. Two analyses done, there is a final analysis pending. Response rate of over 20%, that was with belzutifan, compared to 2% with everolimus, that’s clinically relevant, statistically significant. What we have seen is improvement in the patient reported outcomes and quality of life with belzutifan over everolimus.

I think this drug will likely go through regulatory approval, at least I can speak for the US, because of the results. The results are really quite good, we want to bring these to patients. One of the endpoints was met. In this space of post-PD-1, post-VEGF, we do not have much standard or many options. So I’m happy to see a phase III done in this space and happy for the patients. Hopefully we will see more data from LITESPARK-005 that could continue to define kidney cancer therapies. I’m excited to see updated results, final overall survival, and I’m excited to see more biomarkers to see if we can pick those patients that may benefit from  HIF2 inhibitors.