Keytruda + chemotherapy significantly improved progression-free survival compared to chemotherapy alone as first-line therapy for advanced or recurrent endometrial carcinoma, regardless of mismatch repair status.- Merck Inc.,
Merck Inc., known as MSD outside of the United States and Canada, announced results from the Phase III NRG GY018 trial investigating Keytruda, Merck’s anti-PD-1 therapy, in combination with standard of care chemotherapy (carboplatin and paclitaxel) then continued as a single agent every six weeks for up to 14 cycles for the first-line treatment of patients with stage III-IV or recurrent endometrial carcinoma whose cancer was either mismatch repair proficient (pMMR) or mismatch repair deficient (dMMR).
Results from the trial showed the Keytruda regimen demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients, regardless of mismatch repair status. These late-breaking data are being presented for the first time during a scientific plenary at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer (abstract #338166) and are also being simultaneously published in the New England Journal of Medicine. The results are being discussed with regulatory authorities worldwide.
In the pMMR cohort of 591 evaluable patients, after a median follow-up of 7.9 months, the Keytruda regimen significantly reduced the risk of disease progression or death by 46% (HR=0.54 [95% CI, 0.41-0.71]; p<0.00001) compared to chemotherapy alone; median pfs was 13.1 months (95% ci, 10.5-18.8) for the keytruda regimen versus 8.7 months (95% ci, 8.4-10.7) for chemotherapy alone. in the dmmr cohort of 225 evaluable patients, after a median follow-up of 12 months, the keytruda regimen significantly reduced the risk of disease progression or death by 70% (hr="0.30" [95% ci, 0.19-0.48]; p><0.00001) compared to chemotherapy alone; median pfs was not reached (95% ci, 30.6-nr) for the keytruda regimen versus 7.6 months (95% ci, 6.4-9.9) for chemotherapy alone.></0.00001)></0.00001)>
“Endometrial cancer is the most common type of gynecological cancer, and patients with advanced stage or recurrent disease face a poor prognosis with limited treatment options,” said Dr. Ramez Eskander, principal investigator and gynecologic oncologist, University of California San Diego, Moores Cancer Center. “The significant improvement in progression-free survival regardless of mismatch repair status observed in this study demonstrates the potential of this pembrolizumab regimen to benefit these patients.”
The safety profile of Keytruda in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Grade 3-5 adverse events (AEs) occurred in 55.1% of patients receiving the Keytruda regimen and 45.3% of patients receiving chemotherapy alone in the pMMR cohort. In the dMMR cohort, Grade 3-5 AEs occurred in 63.3% of patients receiving the Keytruda regimen and 47.2% of patients receiving chemotherapy alone. There were no Keytruda-related AEs leading to death in either cohort.
This trial was sponsored by the U.S. National Cancer Institute (NCI), part of the National Institutes of Health. NRG Oncology designed and led the trial with funding from the NCI and participation from all the National Clinical Trials Network (NCTN) Groups. Merck provided funding and support through a Cooperative Research and Development Agreement (CRADA) between Merck and NCI.
In the U.S., Keytruda has two approved indications in endometrial cancer: in combination with Lenvima (lenvatinib), in collaboration with Eisai, for the treatment of patients with advanced endometrial carcinoma that is pMMR, as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation; and as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Merck has a comprehensive clinical development program in breast and gynecological (ovarian, cervical, and endometrial) cancers, comprised of more than 20 Merck-sponsored Phase III studies evaluating Keytruda as monotherapy and in combination with other medicines. In endometrial cancer, Merck is evaluating Keytruda in first-line advanced endometrial cancer both as monotherapy (KEYNOTE-C93/ENGOT-en15/GOG-3064) and in combination with Lenvima (LEAP-001/ENGOT-en9), as well as in the adjuvant setting (KEYNOTE-B21/ENGOT-en11/GOG-3053).
About NRG GY018 NRG GY018 is a randomized, blinded, placebo-controlled Phase III trial (ClinicalTrials.gov, NCT03914612) evaluating Keytruda in combination with standard of care chemotherapy (paclitaxel and carboplatin) versus placebo plus standard of care chemotherapy for the treatment of measurable stage III, IVA, IVB or recurrent endometrial cancer in pMMR and dMMR cohorts. The primary endpoint is PFS, and secondary endpoints include overall survival, objective response rate, duration of response and safety. The trial enrolled 816 patients who were randomized to receive Keytruda plus chemotherapy every three weeks for approximately six cycles followed by Keytruda as a single agent every six weeks for up to 14 cycles, or placebo plus chemotherapy. Enrolled patients were required to have MMR IHC testing prior to randomization; 591 patients were determined to have pMMR tumors, and 225 were determined to have dMMR tumors.
See- "Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer"-Ramez N. Eskander, M.D., Michael W. Sill, Ph.D., Lindsey Beffa, M.D., Richard G. Moore, M.D., et al.-March 27, 2023. DOI: 10.1056/NEJMoa2302312.
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