Pembrolizumab plus chemotherapy appears to produce a significant improvement in progression-free survival among patients with advanced or recurrent endometrial cancer.
Treatment with pembrolizumab (Keytruda) in combination with chemotherapy yielded a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy alone among patients with stage III/IV or recurrent endometrial cancer regardless of mismatch repair status, according to a press release on results from a pre-specified analysis of the phase 3 NRG-GY018 trial (NCT03914612).1
A review conducted by independent data monitoring committee indicated that the regimen, consisting of pembrolizumab plus chemotherapy followed by pembrolizumab monotherapy every 6 weeks up to 14 cycles, met the study’s primary end point of PFS. In the trial, the safety profile for pembrolizumab was comparable with data from previously reported studies. There were no new safety signals associated with the agent.
Investigators will present the full results at an upcoming scientific conference and discuss them with regulatory authorities.
Investigators of the randomized, blinded, placebo controlled phase 3 NRG-GY018 trial compared pembrolizumab plus standard-of-care chemotherapy with placebo plus chemotherapy among a total of 819 patients with measurable stage III, IVa, or IVb, or recurrent endometrial cancer in dMMR and pMMR subgroups.
In the experimental arm, patients received pembrolizumab intravenously for over 30 minutes with intravenous paclitaxel over 3 hours and intravenous carboplatin over 30 minutes on day 1 of each cycle. Treatment repeated every 3 weeks for 6 cycles or until disease progression or unacceptable toxicity. Patients in the comparator arm received matched placebo plus the same chemotherapy backbone.
The primary end point of the trial was PFS. Secondary end points included overall survival, objective response rate, duration of response, and safety.
Patients 18 years and older with measurable advanced or recurrent endometrial cancer and a pathology report with results from an institutional MMR immunohistochemistry test were eligible for enrollment. Additional inclusion criteria included having histologic confirmation of endometrioid adenocarcinoma, serous adenocarcinoma, dedifferentiated or undifferentiated carcinoma, clear cell adenocarcinoma, or mixed epithelial carcinoma; an ECOG performance status of 0 to 2; and receiving prior radiation therapy for endometrial cancer.
Patients who had received prior treatment with an anti–PD-L1 or anti–CTLA-4 agent or a history of severe hypersensitivity to monoclonal antibodies or pembrolizumab were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had untreated central nervous system metastases, active autoimmune disease or history of autoimmune disease that may recur, rheumatoid arthritis or other arthropathies, or a history of non-infectious pneumonitis requiring steroids.
Investigators are also assessing single-agent pembrolizumab as first-line treatment for advanced endometrial cancer in the phase 3 KEYNOTE-C93/ENGOT-en15/GOG-3064 trial (NCT05173987), in combination with lenvatinib (Lenvima) in the phase 3 LEAP-001/ENGOT-en9 trial (NCT03884101), and in the adjuvant setting in the phase 3 KEYNOTE-B21/ENGOT-en11/GOG-3053 trial (NCT04634877).
The FDA approved pembrolizumab for microsatellite instability–high or MMRd advanced endometrial cancer after previous treatment with systemic therapy in any setting.2