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Lenvatinib–Pembrolizumab Boost Advanced Endometrial Cancer Survival

Lenvatinib plus pembrolizumab offer significantly longer survival than chemotherapy for advanced endometrial cancer patients who have progressed after platinum-based chemotherapy
20 Jan 2022
Anticancer Agents;  Endometrial Cancer;  Immunotherapy

Author: By Lynda Williams, Senior medwireNews Reporter 


medwireNews: Lenvatinib plus pembrolizumab significantly improve survival for previously treated patients with advanced endometrial cancer compared with a physician’s choice of chemotherapy, phase III trial results show. 

Reporting that the survival benefits were found in the full study population and among patients with mismatch repair-proficient (pMMR) disease, Vicky Makker, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-workers say that “these results address a need for effective therapy in these patient populations.” 

The Study 309–KEYNOTE-775 trial included 827 patients with advanced, recurrent or metastatic endometrial cancer who had experienced progression after one platinum-based chemotherapy regimen, or two regimens including a neoadjuvant or adjuvant treatment, and who had not received treatment targeting VEGF or PD-1. 

The participants were randomly assigned to receive lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks (n=411), or chemotherapy (n=416) consisting of doxorubicin 60 mg/m2 every 3 weeks or paclitaxel 80 mg/m2 once a week for three out of every 4 weeks.  

At the final progression-free survival (PFS) analysis and the interim overall survival (OS) analysis, the lenvatinib plus pembrolizumab arm was followed up for a median of 12.2 months versus 10.7 months for the chemotherapy arm. 

As reported in The New England Journal of Medicine, patients given lenvatinib plus pembrolizumab had a significantly better outcome than those given chemotherapy for both median PFS (7.2 vs 3.8 months, hazard ratio [HR]=0.56) and median OS (18.3 vs. 11.4 months, HR=0.62). 

When the researchers considered only the 697 patients with pMMR disease, lenvatinib plus pembrolizumab was again associated with significantly better median PFS (6.6 vs 3.8 months, HR=0.60) and median OS (17.4 vs 12.0 months, HR=0.68) than chemotherapy. 

“The efficacy curves separated early during the course of trial therapy and remained consistently separated throughout the evaluation period”, the authors comment, adding that survival benefits occurred across all subgroups including in patients with rare but aggressive histology. 

Vicky Makker and co-workers also highlight that the “prolonged” OS with lenvatinib plus pembrolizumab occurred despite 9.1% of chemotherapy-treated patients with pMMR disease subsequently receiving the combination treatment and 16.9% of patients with MMR-deficient disease going on to receive anti-PD-1 pathway treatment alone or with other agents. 

The safety profile for the combination arm was “generally consistent” with previously reported adverse events (AEs) for the combination and the individual agents, the researchers say. 

The median duration of treatment was 231 days for the combination arm versus 104 days for chemotherapy, with more patients in the combination arm versus chemotherapy arm continuing treatment for at least 6, 12 and 18 months. 

Grade 3 or more severe AEs occurred in 88.9% of patients receiving lenvatinib plus pembrolizumab versus 72.7% of those given chemotherapy, with grade 5 AEs reported for 5.7% and 4.9% of the groups, respectively. 

The investigators say that hypothyroidism was the most common AE of special interest for pembrolizumab, affecting 57.6% of patients, mostly at grade 1 or 2, and “was detected by means of surveillance and corrected easily with oral medication.” 


Makker V, Colombo N, Casado Herráez C, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med; Advance online publication 19 January 2022. Doi: 10.1056/NEJMoa2108330

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2022 Springer Healthcare part of the Springer Nature group

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