At ESMO2020's presidential session I, the first results of the CheckMate-9ER study were presented by Prof. Tony Chouieri from the Dana Farber Cancer Institute.
CheckMate-9ER is a randomised controlled trial comparing the combination of nivolumab and cabozantinib versus the long-standing standard sunitinib as first-line treatment for metastatic renal cell carcinoma with a clear cell component and any IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) risk group. In this first analysis, superiority of the combination of nivolumab/cabozantinib over sunitinib was shown meeting all three efficacy end points. Progression-free survival, overall survival and objective response rate were all improved with remarkable statistical significance across all predefined subgroups including IMDC risk groups, PD-L1 status (<1% or ≥1%) and bone metastasis. At the same time, safety profiles of both arms were comparable and quality of life (QoL) was in favour of the combination arm.
With these impressive results, nivolumab/cabozantinib will be another new standard first-line option and is expected to be approved by the regulatory authorities soon. Together with nivolumab plus ipilimumab (CheckMate-214 trial) and pembrolizumab plus axitinib (Keynote-426 trial), there are now three combination treatment approaches available for the treatment of IMDC intermediate- and poor-risk clear-cell renal cell carcinoma patients, all of which achieved an improvement of overall survival over the former gold standard of sunitinib. For IMDC good risk patients, pembrolizumab/axitinib and nivolumab/cabozantinib are the new options of choice, as nivolumab/ipilimumab failed to prove superiority over sunitinib in this subset of patients.
Open questions remain with regards to (i) the optimal dose for cabozantinib, which was applied in the lower dose of 40 mg once daily continuously in the CheckMate-9ER study, (ii) decision making towards one or the other combination treatment option, and (iii) the optimal sequencing of the various available treatment options in second and further line treatment. Unfortunately, randomised trials between either of the new treatment standards will likely never be available.
Funding
None declared.
Acknowledgments
Disclosure
MK has nothing to declare. CO: honoraria/presentations: Ipsen Pharma, Roche, Medac; research support: Roche, Pharma Mar; travel grants: Ipsen, PharmaMar, Medac.
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