Pembrolizumab Improves Progression-Free Survival in Endometrial Carcinoma

Pembrolizumab (Keytruda; Merck) plus chemotherapy was highly effective in improving progression-free survival (PFS) compared to chemotherapy alone as first-line therapy for patients with advanced or recurrent endometrial carcinoma, regardless of mismatch repair status. These results were presented during a scientific plenary at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

Pembrolizumab is an anti-programmed death receptor (PD-1) therapy that improves the ability of the body’s immune system to detect and fight tumor cells. It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, activating T lymphocytes that may affect both tumor cells and healthy cells.

Endometrial carcinoma begins in the inner lining of the uterus and is the most common type of cancer in the uterus. An estimated 66,000 new cases of uterine body cancer and approximately 13,000 deaths from the disease will occur in 2023.

“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 Ramez Eskander, MD, principal investigator and gynecologic oncologist at the 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.”

According to results from the phase 3 NRG-GY018 trial, the combination therapy reduced risk of disease progression or death by 46% in patients whose cancer was mismatch repair proficient (pMMR) and by 70% in patients whose cancer was mismatch repair deficient (dMMR), compared to chemotherapy alone.

In the trial, pembrolizumab was administered in combination with standard of care chemotherapy (carboplatin and paclitaxel) and then continued as a single agent every 6 weeks for up to 14 cycles for the first-line treatment of patients with stage 3 to 4 or recurrent endometrial carcinoma whose cancer was either pMMR or dMMR. Statistically significant and clinically meaningful improvements in progression-free survival were seen regardless of mismatch repair status.

In the pMMR cohort of 591 evaluable patients, after a median follow-up of 7.9 months, the pembrolizumab regimen significantly reduced the risk of disease progression or death by 46% compared to chemotherapy alone. The median PFS was 13.1 months for the combination regimen versus 8.7 months for chemotherapy alone.

In the dMMR cohort of 225 evaluable patients, after a median follow-up of 12 months, the pembrolizumab regimen significantly reduced the risk of disease progression or death by 70% compared to chemotherapy alone. The median PFS was not reached for the combination regimen and was 7.6 months in chemotherapy alone.

The safety profile of pembrolizumab in the trial was consistent with what was observed in previously reported studies and no new safety signals were identified. Grade 3 to 5 adverse events (AEs) occurred in 55.1% of patients receiving the pembrolizumab regimen and 45.3% of those receiving chemotherapy alone in the pMMR cohort. In the dMMR cohort, grade 3 to 5 AEs occurred in 63.3% of patients receiving the pembrolizumab regimen and 47.2% of patients receiving chemotherapy alone.

“Keytruda has become an important treatment option, both as monotherapy and in combination, in certain patients with advanced endometrial cancer who have progressed following prior systemic therapy and are not candidates for surgery or radiation,” said Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, in the press release. “Results from this trial show that Keytruda plus chemotherapy, if approved, may represent an important new first-line immunotherapy option for patients with stage 3-4 disease, and could extend the use of Keytruda to more patients earlier in their treatment journey.”

The NRG-GY018 trial is a randomized, blinded, placebo-controlled phase 3 trial. 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 pembrolizumab plus chemotherapy every 3 weeks for approximately 6 cycles followed by pembrolizumab as a single agent every 6 weeks for up to 14 cycles, or placebo plus chemotherapy.

Pembrolizumab currently has 2 approved indications in endometrial cancer in the United States. Firstly, it is approved in combination with lenvatinib (Lenvima; Eisai) for the treatment of patients with endometrial carcinoma that is pMMR 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. Secondly, it is approved as a single agent for patients with advanced endometrial carcinoma that is MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

REFERENCE

Keytruda (pembrolizumab) Plus 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. News release. Merck. March 27, 2023. Accessed March 28, 2023. https://www.merck.com/news/keytruda-pembrolizumab-plus-chemotherapy-significantly-improved-progression-free-survival-compared-to-chemotherapy-alone-as-first-line-therapy-for-advanced-or-recurrent-endometrial-carcinoma/