Cabozantinib after checkpoint inhibitors demonstrates preliminary efficacy in advanced RCC

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Published: 18 Feb 2023
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Dr Laurence Albiges - Institut Gustave Roussy, Villejuif, France

Dr Laurence Albiges speaks to ecancer at ASCO GU 2023 about her talk on interim results from CaboPoint, a phase 2 study of cabozantinib after checkpoint inhibitor therapy in patients with advanced renal cell carcinoma.

She explains that first line checkpoint inhibitor-based therapy is the standard of care for advanced renal cell carcinoma . However, there is a lack of prospective data for cabozantinib after first line checkpoint inhibitor, which is addressed in this study.

Dr Albiges concludes this interim analysis showed cabozantinib demonstrated preliminary efficacy in patients with advanced renal cell carcinoma after progression on checkpoint inhibitor-based combination therapy, irrespective of first line regimen. The CaboPoint trial is ongoing, with the final analysis anticipated in September 2023.

Here at the ASCO GU ’23 meeting I’m presenting for the first time the CaboPoint study. The standard of care for renal cell carcinoma is combination therapy in front line for clear cell RCC, either IO/IO, namely nivolumab plus ipilimumab, or IO plus VEGF TKI such as axitinib/pembrolizumab, cabozantinib/nivolumab or lenvatinib plus pembrolizumab for instance. The question mark we have is what is the activity of second-line TKI after first-line combination? That’s the question addressed by the CaboPoint study.

The CaboPoint study is a phase II non-randomised study looking at activity and safety of cabozantinib single agent after a first line combination. The study has been conducted in Europe, it has included seven countries and enrolled more than 100 patients. What is being presented at this meeting is the first interim analysis. It’s actually the first 88 patients for which we have more than 3 months follow-up because the primary endpoint of this study is response rate.

So we are reporting a response rate that is reaching 30% at the 3 months analysis, meaning clear activity of cabozantinib. When looking at cohort A, which are the patients treated after nivolumab plus ipilimumab, this response rate is actually reaching more than 32%, while in patients that are treated after a VEGF TKI plus IO combination, and it’s mostly axitinib plus pembrolizumab, the response rate is right above 25%. The safety is as anticipated with cabozantinib single agent.

So, to summarise, CaboPoint is the first prospective study looking at cabozantinib activity after a first-line combination providing a response rate above 30%, or in this range, with no new safety signal.

The CaboPoint study is actually a study that is now providing prospective information on what is routinely performed, meaning using sequential VEGF TKI, here cabozantinib, after first-line combination failure. What we don’t know yet is can we do a better job by combining two drugs. For instance, we’re all eagerly waiting for the CONTACT-03 study which will address the question of sustained PD-L1 inhibition by comparing cabozantinib plus PD-L1 versus cabozantinib alone.