The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2021. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Lenvatinib plus pembrolizumab (len-pembro) can improve survival, when compared with physician’s choice of treatment (TPC), across subgroups of patients with previously treated, advanced endometrial cancer, according to a post hoc analysis of the phase 3 KEYNOTE-775 trial.1

The progression-free survival (PFS) and overall survival (OS) benefits observed with len-pembro were seen regardless of histology, prior (neo)adjuvant therapies, platinum-free interval, or DNA mismatch repair (MMR) status.


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These results were presented at the European Society for Medical Oncology (ESMO) Congress 2021 by Nicoletta Colombo, MD, PhD, of the University of Milan-Bicocca in Milan, Italy.

The KEYNOTE-775 trial (ClinicalTrials.gov Identifier: NCT03517449) enrolled 827 patients with histologically confirmed, previously treated, advanced endometrial cancer.

The researchers randomly assigned 411 patients to receive len-pembro and 416 to receive TPC. The patients were stratified by MMR status, geographic region, and prior pelvic radiation.

A prior analysis showed that len-pembro significantly improved PFS and OS.2 At ESMO 2021, Dr Colombo presented results from a post hoc analysis showing efficacy outcomes by tumor histology, MMR status, and prior therapy.1

Dr Colombo reported that len-pembro conferred a PFS and OS benefit regardless of prior therapy. However, patients who received 1 prior line of platinum-based therapy had more favorable hazard ratios (HRs) for OS and PFS, compared with patients who received more than 1 line of platinum therapy.

This finding supports earlier use of len-pembro, Dr Colombo said. She also reported that len-pembro improved PFS and OS across histologies and regardless of MMR status.

PFS by Histology and MMR Status

In the entire cohort, the median PFS by histology was:

  • 7.6 months with len-pembro and 3.9 months with TPC (HR, 0.52; 95% CI, 0.41-0.65) for patients with endometrioid histology
  • 5.7 months with len-pembro and 3.6 months with TPC (HR, 0.53; 95% CI, 0.38-0.72) for serous histology
  • 3.9 months with len-pembro and 2.0 months with TPC (HR, 0.47; 95% CI, 0.24-0.92) for clear cell histology.

In the MMR-proficient (pMMR) cohort, the median PFS by histology was:

  • 7.6 months with len-pembro and 5.0 months with TPC (HR, 0.59; 95% CI, 0.46-0.76) for patients with endometrioid histology
  • 5.7 months with len-pembro and 3.6 months with TPC (HR, 0.54; 95% CI, 0.39-0.75) for serous histology
  • 3.9 months with len-pembro and 2.0 months with TPC (HR, 0.49; 95% CI, 0.25-0.97) for clear cell histology.

OS by Histology and MMR Status

The median OS by histology in the overall cohort was:

  • Not reached with len-pembro and 13.4 months with TPC (HR, 0.65; 95% CI, 0.49-0.84) for patients with endometrioid histology
  • 12.0 months with len-pembro and 9.3 months with TPC (HR, 0.68; 95% CI, 0.48-0.94) for serous histology
  • 19.9 months with len-pembro and 8.7 months with TPC (HR, 0.33; 95% CI, 0.15-0.74) for clear cell histology.

In the pMMR cohort, the median OS by histology was:

  • 20.0 months with len-pembro and 15.2 months with TPC (HR, 0.78; 95% CI, 0.57-1.05) for patients with endometrioid histology
  • 12.0 months with len-pembro and 10.0 months with TPC (HR, 0.68; 95% CI, 0.49-0.96) for serous histology
  • 19.9 months with len-pembro and 8.7 months with TPC (HR, 0.34; 95% CI, 0.15-0.78) for clear cell histology.

Dr Colombo noted that KEYNOTE-775 was not designed or powered for this post hoc analysis, so “the results should be interpreted with caution.”

Disclosures: This research was supported by Eisai Inc., and Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Read more of Cancer Therapy Advisor’s coverage of ESMO 2021 by visiting the conference page.

References

  1. Colombo N, Lorusso D, Casado A, et al. Outcomes by histology and prior therapy with lenvatinib plus pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer (Study 309/KEYNOTE-775). Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract 726MO.
  2. Makker V, Colombo N, Casado Herráez A, et al. A multicenter, open-label, randomized, phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician’s choice in patients with advanced endometrial cancer. Gynecol Oncol. 2021;162 (suppl 1):S4 https://doi.org/10.1016/S0090-8258(21)00657-0