Combination therapy of pembrolizumab (Keytruda) and lenvatinib (Lenvima) demonstrated a significant and clinically meaningful improvement in progression-free survival in first-line advanced renal cell carcinoma (RCC) patients, according to results from the phase III CLEAR study (KEYNOTE-581/Study 307).
The multi-centre, randomised, trial analysed lenvatinib in combination with pembrolizumab or everolimus versus sunitinib for the first-line treatment of patients with advanced RCC.
The trial had 1,069 participants who were randomised to one of the three treatment arms. They received lenvatinib (20mg orally once daily) plus pembrolizumab (200mg intravenously every three weeks) or lenvatinib (18mg orally once daily) plus everolimus (5mg orally once daily) or sunitinib (50mg orally once daily for four weeks on treatment, followed by two weeks off treatment).
The trial’s primary endpoint involved progression-free survival (PFS) while major secondary endpoints were overall survival (OS), objective response rate (ORR) and safety.
Data showed that pembrolizumab plus lenvatinib significantly lowered the risk of disease progression or death by 61% as compared with sunitinib, with a median PFS of 23.9 months versus 9.2 months for sunitinib.
In the trial’s key secondary endpoints, the combination lowered the risk of death by 34% versus sunitinib arm. The combination treatment also resulted in an ORR of 71% versus 36.1% in the sunitinib arm. Furthermore, lenvatinib plus everolimus also showed statistically significant improvements in PFS and ORR as compared with sunitinib.
Pembrolizumab is Merck’s anti-PD-1 therapy while lenvatinib is the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai.