Real-World Experience with Pembrolizumab Treatment in Patients with Heavily Treated Recurrent Gynecologic Malignancies

Abstract

Purpose: We evaluated the efficacy and safety of pembrolizumab in patients with recurrent gynecologic cancers in real-world practice. Materials and Methods: We conducted a retrospective, single-institution study of patients with recurrent gynecologic malignancies treated with pembrolizumab. The primary endpoints were the objective response rate (ORR) and safety. Results: Thirty-one patients treated with pembrolizumab were included. The primary disease sites were the uterine cervix (n=18), ovaries (n=8), and uterine corpus (n=5). Fifteen of the 31 patients (48%) had an Eastern Cooperative Oncology Group performance status of ≥2. The median number of prior chemotherapy lines was 2 (range, 1-6), and 14 of 31 patients (45%) had received ≥ 3 prior lines of chemotherapy. The overall ORR was 22.6%: specifically, 22.3% (4 of 18 patients), 12.5% (1 of 8 patients), and 40% (2 of 5 patients) for cervical, ovarian, and endometrial cancers, respectively. During a median follow-up of 4.7 months (range, 0.2-35.3), the median time to response was 1.9 months (range, 1.4-5.7). The median duration of response was not reached (range, 8.8-not reached). The median progression-free survival was 2.5 months (95% confidence interval, 1.7-not reached). Adverse events occurred in 20 patients (64.5%), and only 3 (9.7%) were grade ≥3. There was one case of suspicious treatment-related mortality, apart from which most adverse events were manageable. Conclusion: In real-world practice, pembrolizumab was feasible and effective in heavily treated recurrent gynecologic cancer patients with poor performance status who may not be eligible for enrollment in clinical trials.

Pembrolizumab in endometrial cancer: Where we stand now (Review)

“…Overall, 18 reviews (21-38) and 8 case reports (39)(40)(41)(42)(43)(44)(45)(46) were identified, while 40 studies were deemed irrelevant. After removal of ineligible studies, 6 studies were recruited (47)(48)(49)(50)(51)(52). After evaluating the references of the eligible studies, three additional articles were identified (53)(54)(55).…”

“…After evaluating the references of the eligible studies, three additional articles were identified (53)(54)(55). Overall, 9 studies incorporating data from 712 EC patients were eligible for this systematic review (47)(48)(49)(50)(51)(52)(53)(54)(55). The aforementioned process of the selection of studies is illustrated in Fig.…”

“…Five out of nine trials were multicohort including a variety of MSI-H/ dMMR deficient tumors (47,48,51,52,55) while four trials enrolled exclusively endometrial cancer patients (49,50,53,54). Six clinical trials were Phase Ib/II (47,49,(51)(52)(53)55), one was Phase III (54) randomized clinical trial, while two of them were retrospective, single-institution cohort studies (48,50).…”

“…All patients had histologically or cytologically confirmed locally advanced, metastatic or recurrent EC. They had received at least one previous systematic treatment and had evidence of disease progression (47)(48)(49)(50)(51)(52)(53)(54)(55). Five studies evaluated pembrolizumab administration in patients with MSI-H/dMMR advanced EC (48,49,52,53,55), one study focused on PD-L1 positive EC patients (47), while the other studies evaluated pembrolizumab administration in advanced EC irrespective of MSI or PD-L1 status (50,51,54).…”

“…They had received at least one previous systematic treatment and had evidence of disease progression (47)(48)(49)(50)(51)(52)(53)(54)(55). Five studies evaluated pembrolizumab administration in patients with MSI-H/dMMR advanced EC (48,49,52,53,55), one study focused on PD-L1 positive EC patients (47), while the other studies evaluated pembrolizumab administration in advanced EC irrespective of MSI or PD-L1 status (50,51,54). Three studies evaluated the combination of pembrolizumab with lenvatinib in advanced/recurrent EC (50,51,54) whereas the remaining studies evaluated pembrolizumab as a single agent in pretreated PD-L1 positive and/or MSI-H/dMMR advanced EC tumors (47)(48)(49)52,53,55).…”