Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer

Author(s): Vicky Makker, MD1; Matthew H. Taylor, MD2; Carol Aghajanian, MD1; Ana Oaknin, MD, PhD3; James Mier, MD4; Allen L. Cohn, MD5; Margarita Romeo, MD, PhD6; Raquel Bratos, MD7; Marcia S. Brose, MD, PhD8; Christopher DiSimone, MD9; Mark Messing, MD10; Daniel E. Stepan, MD11; Corina E. Dutcus, MD12; Jane Wu, PhD12; Emmett V. Schmidt, MD, PhD13; Robert Orlowski, MD13; Pallavi Sachdev, PhD12; Robert Shumaker, PhD11; and Antonio Casado Herraez, MD, PhD14
Source: DOI: 10.1200/JCO.19.02627 Journal of Clinical Oncology 38, no. 26 (September 10, 2020) 2981-2992. Published online March 13, 2020. PMID: 32167863
Lucio Gordan MD

Dr. Gordan's Thoughts

Another win for combined target-IO Rx with meaningful OS difference and reasonable/expected tolerability.

BACKGROUND

Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear.

METHODS

In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician’s choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair–proficient (pMMR) disease and in all patients. Safety was also assessed.

RESULTS

A total of 827 patients (697 with pMMR disease and 130 with mismatch repair–deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy.

CONCLUSIONS

Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309–KEYNOTE-775 ClinicalTrials.gov number)

Author Affiliations

1Memorial Sloan Kettering Cancer Center, New York, NY 2Oregon Health & Science University, Portland, OR 3Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain 4Beth Israel Deaconess Medical Center, Boston, MA 5Rocky Mountain Cancer Center, Denver, CO 6Catalan Institute of Oncology, B-ARGO, Badalona, Spain 7MD Anderson Cancer Center España, Madrid, Spain 8Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 9Arizona Oncology Associates, Tucson, AZ 10Texas Oncology, Bedford, TX 11Formerly of Eisai Inc., Woodcliff Lake, NJ 12Eisai, Woodcliff Lake, NJ 13Merck & Co. Inc., Kenilworth, NJ 14San Carlos University Teaching Hospital, Madrid, Spain

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