Results of the NeoPembrOV phase 2 trial support the safe addition of pembrolizumab to neoadjuvant chemotherapy in patients deemed nonoptimally resectable. Although the addition of pembrolizumab resulted in an improved complete resection rate, it did not provide a progression-free survival benefit.
The multicenter, open-label, noncomparative, randomized NeoPembrOV phase 2 trial investigated the efficacy and safety of adding pembrolizumab to neoadjuvant carboplatin/paclitaxel chemotherapy after interval debulking surgery (IDS) and standard systemic therapy in patients with initially unresectable high-grade serous carcinoma (HGSC). The results of this study were reported at the 2021 American Society of Clinical Oncology Annual Meeting.
The study enrolled patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV ovarian, tubal, or primary peritoneal HGSC, with a ≤8-week interval between diagnosis and enrollment. These patients may have been denied up-front complete debulking surgery, and cytoreduction would have been anticipated with the goal of no residual disease planned at IDS. Eligible patients were randomized (2:1) to receive 4 cycles of pembrolizumab with or without carboplatin/paclitaxel before IDS, followed by postoperative chemotherapy (2-4 cycles) and optional bevacizumab for 15 months in total, with or without pembrolizumab as maintenance therapy for up to 2 years. Stratification was based on center, FIGO stage, bevacizumab planned after IDS, and disease volume (<5 cm/>5 cm). The primary end point was centrally reviewed complete resection rate (CRR) at IDS; secondary end points were safety, surgical morbidity, overall response rate (ORR), progression-free survival (PFS), and overall survival.
From February 2018 to April 2019, 91 patients were enrolled in the study; of these, 61 patients were in the carboplatin/paclitaxel plus pembrolizumab group, and 30 were in the carboplatin/paclitaxel group. The median age of the study population was 63 years, and the median peritoneal cancer index was 24; the majority had FIGO stage IIIC (82.4%) and either used or anticipated the use of bevacizumab (91%). Eighty (88%) patients received bevacizumab plus carboplatin/paclitaxel, followed by bevacizumab with or without pembrolizumab in maintenance.
In the carboplatin/paclitaxel plus pembrolizumab group (n = 61), 58 (95%) patients had IDS and 78% achieved complete resection. The CRR achieved in the carboplatin/paclitaxel plus pembrolizumab group was 74%; and that in the carboplatin/paclitaxel group was 70%. Higher ORRs were achieved before IDS in the carboplatin/paclitaxel plus pembrolizumab group versus the carboplatin/paclitaxel group (76% vs 61%). No PFS benefit was observed with the addition of pembrolizumab to neoadjuvant chemotherapy.
The incidence of grade ≥3 adverse events (AEs) was similar in the carboplatin/paclitaxel plus pembrolizumab and carboplatin/paclitaxel groups (75.4% vs 66.7%); the more frequent AEs in the carboplatin/paclitaxel plus pembrolizumab group were neutropenia (13.1%), anemia (4.9%), thrombopenia (3.3%), high blood pressure (3.3%), and pulmonary embolism (3.3%). Postoperative complications occurred in 21.3% of patients in the carboplatin/paclitaxel plus pembrolizumab group, compared with 13.3% in the carboplatin/paclitaxel group.
These results support the safe addition of pembrolizumab to neoadjuvant chemotherapy in patients deemed nonoptimally resectable, which resulted in improved CRR, but did not provide PFS benefit.
Source: Ray-Coquard IL, Savoye AM, Mouret-Reynier MA, et al. Efficacy and safety results from neopembrov study, a randomized phase II trial of neoadjuvant chemotherapy (CT) with or without pembrolizumab (P) followed by interval debulking surgery and standard systemic therapy ± P for advanced high-grade serous carcinoma (HGSC): a GINECO study. J Clin Oncol. 2021;39(suppl_15). Abstract 5500.