Merck & Co. and Eisai announced detailed results from the Phase III CLEAR study, showing that the combination of Keytruda (pembrolizumab) and Lenvima (lenvatinib) significantly reduced the risk of disease progression or death by 61% versus Pfizer's Sutent (sunitinib) for the first-line treatment of patients with advanced renal cell carcinoma (RCC). The data were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).
The trial, also known as KEYNOTE-581/Study 307, randomised 1069 patients with advanced RCC to receive first-line treatment with the tyrosine kinase inhibitor Lenvima in combination with either the anti-PD-1 therapy Keytruda or everolimus, or Sutent alone. The study's primary endpoint is progression-free survival (PFS), while key secondary goals include overall survival (OS) and objective response rate (ORR).
Merck and Eisai reported in November last year that the trial met its main endpoint, as well as the key secondary goals. Results detailed at ASCO GU, and also published in the NEJM, demonstrated that Keytruda in combination with Lenvima was associated with a median PFS of 23.9 months, compared to 9.2 months for Sutent alone and 14.7 months for Lenvima plus everolimus. Meanwhile, although median OS was not reached in either treatment arm after a median follow-up of 27 months, it was longer with the combination of Keytruda and Lenvima versus Sutent, but not with Lenvima plus everolimus (see table below).
Lead investigator Robert Motzer, who suggested that the results have "the potential to impact clinical practice," said "Keytruda plus Lenvima demonstrated a median [PFS] of nearly two years, and seven in 10 patients experienced an objective response." Motzer added "this combination also significantly improved [OS] compared with [Sutent], with a 34% reduction in risk of death." For further analysis, read ViewPoints: It becomes CLEAR that Keytruda/Lenvima is another potent RCC combo.
The companies noted that the safety profiles of both Keytruda and Lenvima were consistent with previously reported studies. Results showed that treatment-related adverse events of at least grade 3 occurred at rates of 71.6% in patients on Keytruda plus Lenvima, 73% in those given Lenvima and everolimus, versus 58.8% for Sutent alone.
Keytruda is currently cleared in the US and Europe in combination with Pfizer's tyrosine kinase inhibitor Inlyta (axitinib) as a first-line treatment for patients with advanced RCC. Last month, the FDA approved the combination of Bristol Myers Squibb's anti-PD-1 antibody Opdivo (nivolumab) and Exelixis' tyrosine kinase inhibitor Cabometyx (cabozantinib) as a first-line treatment for patients with advanced RCC. That combination is also under review in the EU and Japan.
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