Lenvatinib plus pembrolizumab improves survival outcomes in advanced endometrial cancer
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Lenvatinib plus pembrolizumab conferred significantly longer PFS and OS than chemotherapy among women with advanced endometrial cancer, according to randomized, phase 3 trial results published in The New England Journal of Medicine.
The latest findings of KEYNOTE-775/Study 309 showed benefits “both [among women with mismatch repair-proficient disease] and in the overall trial population of patients with advanced endometrial cancer who had disease progression after the receipt of previous systemic platinum-based therapy,” Vicky Makker, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues wrote.
Background
Makker and colleagues pursued the research because incidence of endometrial cancer is increasing worldwide — with approximately 10% to 15% of women presenting with advanced disease — and because the standard therapy for advanced endometrial cancer after the failure of platinum-based chemotherapy remains unclear.
In 2019, the FDA granted accelerated approval of the combination of lenvatinib (Lenvima, Eisai) and pembrolizumab (Keytruda, Merck) for treatment of women with advanced endometrial carcinoma who did not have microsatellite instability-high or mismatch repair-deficient disease had progressed after prior systemic therapy and were not candidates for curative surgery or radiation.
Methodology
KEYNOTE-775/Study 309 included 827 women with advanced endometrial cancer (697 mismatch repair-proficient, 130 mismatch repair-deficient) who previously received at least one platinum-based chemotherapy. Researchers randomly assigned the women 1:1 to receive 20 mg oral lenvatinib once a day plus 200 mg pembrolizumab via IV every 3 weeks (n = 411) or chemotherapy that consisted of either 60 mg/m2 doxorubicin via IV every 3 weeks or 80 mg/m2 paclitaxel via IV weekly in a 3-weeks-on, 1-week-off cycle (n = 416).
OS and PFS — the latter assessed by blinded independent central review per RECIST version 1.1 — served as the primary endpoints.
Key findings
Results showed longer median PFS with lenvatinib plus pembrolizumab vs. chemotherapy among women with mismatch repair-proficient disease (6.6 months vs. 3.8 months; HR = 0.6; 95% CI, 0.5-0.72), as well as the overall population (7.2 months vs. 3.8 months; HR = 0.56; 95% CI, 0.47-0.66).
Additionally, researchers reported longer median OS with the lenvatinib-pembrolizumab combination among both groups (mismatch repair-proficient disease, 17.4 months vs. 12 months; HR = 0.68; 95% CI, 0.56-0.84; overall population, 18.3 months vs. 11.4 months; HR = 0.62; 95% CI, 0.51-0.75).
Safety analyses showed grade 3 or higher adverse events occurred among 88.9% of the lenvatinib-pembrolizumab group vs. 72.7% of those who received chemotherapy.
Researchers wrote that trial limitations included “a relatively short duration of follow-up, which may mean that responses are evolving.” Safety and efficacy monitoring is ongoing, they added, even with the protocol-specified criteria reached in the trial’s efficacy analyses.
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