How do you reconcile the lack of OS benefit in the CLEAR trial comparing Lenvatinib + Pembrolizumab to Sunitinib, to the very impressive ORR and mPFS benefit seen?

At the primary analysis point of the phase III open-label, CLEAR study (Study 307/KEYNOTE-581), with a median survival follow-up of 26.6 months, lenvatinib plus pembrolizumab showed superior efficacy versus sunitinib in the first-line treatment of patients with advanced renal cell carcinoma. (Motzer et al., PMID 33616314)

With an additional follow-up of 23 months from the primary analysis, at the data cut-off date of July 31, 2022, updated survival data results were reported as a 36-month overall survival (OS) rate of 66.4% with lenvatinib plus pembrolizumab versus 60.2% with sunitinib with an OS HR of 0.79 (95% CI, 0.63 to 0.99) representing a 21% reduction in the risk of death. (Motzer et al., PMID 38227898)

Fewer patients in the lenvatinib...