Combination extends OS in advanced endometrial cancer
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Pembrolizumab plus lenvatinib improved outcomes compared with chemotherapy for women with advanced endometrial cancer, according to topline data released by the agents’ manufacturers.
Women assigned the combination achieved longer OS and PFS and were more likely to respond to therapy, results of the randomized phase 3 KEYNOTE-775/Study 309 trial showed.
Pembrolizumab (Keytruda, Merck) is an anti-PD-1 antibody, and lenvatinib (Lenvima, Eisai) is a multiple receptor tyrosine kinase inhibitor.
The FDA granted accelerated approval to the combination in 2019 for treatment of women with advanced endometrial carcinoma that is not microsatellite instability-high or mismatch repair deficient, or whose disease progressed after prior systemic therapy and who are not candidates for curative surgery or radiation.
The multicenter, open-label KEYNOTE-775/Study 309 trial included 827 women with advanced endometrial cancer who received at least one prior platinum-based regimen.
Researchers assigned women in the experimental group to pembrolizumab dosed at 200 mg via IV every 3 weeks for up to 35 cycles plus lenvatinib dosed at 20 mg orally once daily. Women in the control group received physicians’ choice of IV doxorubicin dosed at 60 mg/m2 every 3 weeks for a maximum cumulative dose of 500 mg/m2, or IV paclitaxel dosed at 80 mg/m2 in 28-day cycles (3 weeks on, 1 week off).
OS and PFS as assessed by blinded independent central review served as the primary endpoints. Secondary endpoints included objective response rate by blinded independent central review and safety/tolerability.
The study met its primary endpoints, as well as the secondary endpoint of improved ORR, with the pembrolizumab-lenvatinib combination.
Researchers observed the benefit of the combination in the subgroup of women with mismatch repair-proficient tumors, as well as in the intention-to-treat population, which included women with endometrial cancer that was mismatch repair proficient and those whose disease was microsatellite instability-high/mismatch repair deficient.
The combination exhibited a safety profile consistent with that observed in prior studies.
Full results of the trial will be submitted for presentation at a medical meeting. Representatives of Merck and Eisai will discuss these results with regulatory authorities.
“Women with advanced endometrial cancer are faced with high mortality rates and limited treatment options following initial systemic therapy,” Gregory Lubiniecki, MD, associate vice president for oncology clinical research at Merck Research Laboratories, said in a company-issued press release. “These are the first results from a phase 3 trial of a combination regimen including immunotherapy in advanced endometrial carcinoma that have shown a statistically significant improvement in overall survival, progression-free survival and objective response rate vs. chemotherapy.”
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