Lenvatinib plus pembrolizumab prolongs survival in renal cell carcinoma

A phase 3 trial discovered statistically significant prolonged progression-free survival (PFS) and objective response rates (ORR) in patients with renal cell carcinoma (RCC) treated with lenvatinib plus pembrolizumab versus patients treated with sunitinib alone. Overall survival (OS) was prolonged in patients receiving lenvatinib plus pembrolizumab, but not in those receiving lenvatinib plus everolimus compared with sunitinib. Safety of these combinations was deemed equivalent to the safety profiles of the individual agents.

Dr Robert Motzer (Memorial Sloan Kettering Cancer Centre, New York, USA) presented the results of the CLEAR trial (NCT02811861) [1,2]. This was a multi-centre, randomised, open-label phase 3 trial comparing the efficacy and safety of combination therapy lenvatinib plus either pembrolizumab or everolimus with that of single therapy sunitinib as first-line therapy for patients with advanced RCC. Patients (n=1,069) were randomised 1:1:1 to 1 of 3 treatment arms.

The primary endpoint was PFS as determined by an independent review committee. At the median follow up at 27 months, PFS was significantly longer in the lenvatinib plus pembrolizumab arm compared with the sunitinib arm (median 23.9  months vs 9.2 months; HR 0.39; 95% CI 0.32–0.49; P<0.001). PFS was also significantly longer in the lenvatinib plus everolimus treatment arm than in the sunitinib arm (median 15 months vs 9 months; HR 0.65; 95% CI 0.53–0.80; P<0.001).

Secondary endpoints included OS and ORR. OS was significantly lengthened in the lenvatinib plus pembrolizumab group (HR 0.66; 95% CI 0.49–0.88; P=0.005), but not in the lenvatinib plus everolimus group (HR 1.15; 95% CI 0.88–1.50; P=0.3). ORR was significantly improved in both dual therapy arms: in the lenvatinib plus pembrolizumab arm, ORR was 71% with a complete response rate of 16%; in the lenvatinib plus everolimus arm, ORR was 54% with a complete response rate of 10%; in the sunitinib arm, ORR was 36%, with a complete response rate of 4% (OR 2.15; 95% CI 1.57–2.93).

1. Motzer R. Phase 3 trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) monotherapy as a first-line treatment for patients (pts) with advanced renal cell carcinoma (RCC) (CLEAR study). Abstract 269, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.
2. Motzer R, et al. N Engl J Med. 2021 Feb 13. DOI: 10.1056/NEJMoa2035716. Online ahead of print.

 

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Posted on 24 March 202118 June 2021