Pembrolizumab monotherapy in Japanese patients with advanced ovarian cancer: Subgroup analysis from the KEYNOTE‐100

Abstract

Interim results from the two-cohort, phase 2 KEYNOTE-100 study (NCT02674061) of 376 patients with previously treated advanced recurrent ovarian cancer (ROC) showed that pembrolizumab monotherapy was associated with an objective response rate (ORR) of 8.0% (95% CI, 5.4-11.2). We present outcomes for the Japanese patients (n = 21) enrolled in KEYNOTE-100. Patients with epithelial ROC had received either 1-3 prior chemotherapy lines and had platinum-free interval or treatment-free interval (PFI; TFI) of 3-12 months (cohort A) or 4-6 prior chemotherapy lines and had PFI/TFI of ≥3 months (cohort B). All patients received pembrolizumab 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity or consent withdrawal. Primary objectives were ORR per RECIST v1.1 for each cohort and higher programmed death ligand-1 (PD-L1) tumor expression. The relationship between PD-L1 expression (measured as combined positive score [CPS]) and ORR was assessed.Twenty-one Japanese patients (cohort A, n = 19; cohort B, n = 2) were treated. The median (range) age was 57 (37-78) years; 19 (90.5%) patients had ECOG status of 0 and 16 (76.2%) patients had stage III-IV disease. ORR was 19.0% (95% CI, 5.4-41.9) and seemed to increase with increasing PD-L1 expression. A total of 13 (61.9%) patients had treatment-related adverse events (TRAE), and 5 (23.8%) had grade 3-4 TRAE.There were no treatment-related deaths in this subpopulation. Pembrolizumab monotherapy was associated with antitumor activity in Japanese patients with ROC, with no new safety signals identified in this subpopulation. The data suggested a trend toward higher PD-L1 expression among some patients with higher ORR. K E Y W O R D Scombined positive score, objective response rate, ovarian cancer, PD-L1, pembrolizumab | 1325 NISHIO et al.

Comprehensive Analyses Identify APOBEC3A as a Genomic Instability-Associated Immune Prognostic Biomarker in Ovarian Cancer

“…Currently, emerging data have reported that ICB immunotherapy could be hopeful for OC patients with recurrence (49). A variety of previously published literatures have reported that OC patients who met the following criteria could probably benefit more from immunotherapy using anti-PD-1/PD-L1 antibodies: (i) highly expressed in PD-L1, (ii) high microsatellite instability (MSI-H), (iii) defective mismatch DNA repair (dMMR), (iv) high tumorinfiltrating lymphocytes with high TMB, and (v) T-cell inflammatory gene expression profile (GEP) (50)(51)(52). Disappointingly, the overall response rate of immunotherapy was still unsatisfactory since the TME of OC was generally in a state of immunosuppression (22).…”

Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment

“…However, a subgroup of these patients with tumours positive for PD-L1, CD8+ infiltrates or both exhibited a significant survival benefit with combination treatment [ 41 ]. Pembrolizumab monotherapy for advanced OC also resulted in a greater ORR in patients with PD-L1 expression, identifying a subpopulation for future ICB OC studies [ 43 ].…”

Complete remission of heavily treated ovarian clear cell carcinoma with ARID1A mutations after pembrolizumab and bevacizumab combination therapy: a case report

“…Her unexpected excellent response supports the need to identify other theranostic biomarkers for checkpoint inhibitors [ 1 ]. Because OCCC is prevalent in Asia [ 7 ], a subgroup analysis of 21 Japanese patients with OCCC in the KEYNOTE-100 trial revealed a better objective response rate of these patients (19.0, 95% CI: 5.4–41.9). The hypothesis and the reasons why OCCC showed a better response to immune checkpoint inhibitors require further investigation.…”