# KEYNOTE-775: lenvatinib plus pembrolizumab versus chemotherapy for previously treated advanced endometrial cancer

Source: https://onco.cc/key-papers/paper-keynote-775-nejm-2022/  
OnCo record `paper-keynote-775-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

After platinum chemotherapy, the combination of the kinase inhibitor lenvatinib and pembrolizumab lengthened survival compared with doxorubicin or paclitaxel in advanced endometrial cancer, including in the mismatch repair-proficient majority.

## Summary

Phase 3 trial of 827 patients with advanced endometrial cancer after one prior platinum regimen randomised to lenvatinib plus pembrolizumab or physician's choice of doxorubicin or weekly paclitaxel.

In mismatch repair-proficient disease median overall survival was 17.4 versus 12.0 months (hazard ratio 0.68) and median progression-free survival 6.6 versus 3.8 months; results were similar in the whole population. Grade 3 or higher adverse events occurred in 89 percent of the combination arm.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2108330
- Authors: Makker V, Colombo N, Casado Herráez A, et al.
- Findings: Mismatch repair-proficient: median overall survival 17.4 vs 12.0 months; hazard ratio 0.68.; All patients: median overall survival 18.3 vs 11.4 months; hazard ratio 0.62.
- What it means: Lenvatinib-pembrolizumab is the standard second-line treatment for mismatch repair-proficient endometrial cancer after platinum, though its toxicity is considerable and its place after first-line immunotherapy is unclear.
- Caveats: Hypertension, hypothyroidism, diarrhoea and weight loss led to frequent dose reductions.; Patients had not received prior immunotherapy, unlike many today.

## Sources

- N Engl J Med 2022: https://doi.org/10.1056/NEJMoa2108330
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35045221/

## Connected records

- cancers: [Advanced or recurrent endometrial cancer](https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/)
- drugs: [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- trials: [KEYNOTE-775 / Study 309](https://onco.cc/trials/keynote-775/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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