Valerie Heong

Durvalumab versus Physician’s Choice Chemotherapy in Recurrent Ovarian Clear Cell Adenocarcinoma (MOCCA/APGOT-OV2/GCGS-OV3): A Multicenter, Randomized, Phase 2 Trial

Abstract Purpose: The optimal treatment of recurrent ovarian clear cell carcinoma (rOCCC) remains unknown. This is the first randomized trial to compare durvalumab with chemotherapy in rOCCC. Patients and Methods: MOCCA is a randomized, phase 2 trial conducted in Singapore, Korea, and Australia. Eligible patients had rOCCC with recurrence after platinum-based chemotherapy, Eastern Cooperative Oncology Group performance status ≤2, and no prior immune checkpoint blockade. Patients were randomly assigned (2:1) to durvalumab (1,500 mg every 4 weeks) or chemotherapy. Patients progressing on chemotherapy were allowed to cross over to durvalumab. The primary outcome was progression-free survival. Secondary outcomes included overall survival, objective response rates, and safety. Results: Forty-eight eligible women were assigned to durvalumab (N = 31) or chemotherapy (N = 17). The median progression-free survival was 7.6 [95% confidence interval (CI), 7.0–16.0] and 14.0 (95% CI, 7.0–32.9) weeks with durvalumab and chemotherapy, respectively (HR = 1.6; 95% CI, 0.8–3.0; P = 0.92). The median overall survival was 37.9 (95% CI, 21.7–143.0) and 40.6 (95% CI, 25.0–not reached) weeks, respectively (HR = 1.5; 95% CI, 0.7–3.3; P = 0.85). The difference in objective response rates between the groups was not statistically significant (durvalumab 9.7% vs. physician’s choice chemotherapy 18.8%; difference −9.1%; 95% CI, −31.3% to 12.9%; P = 0.83). Fewer all-grade (35.5% vs. 68.8%) and high-grade (9.7% vs. 31.3%) treatment-related adverse events were observed for durvalumab. PD-L1 combined positive score (CPS)+ was observed in 28.9% (CPS ≥1%) and 10.5% (CPS ≥10%) of patients. PIK3CA mutations were associated with time to progression on durvalumab ≥12 weeks [relative risk (mutated vs. wild-type) 2.83; 95% CI, 1.16–14.17]. Conclusions: Durvalumab was well-tolerated but did not improve efficacy outcomes compared with chemotherapy in rOCCC.

A multi‐ethnic analysis of immune‐related gene expression signatures in patients with ovarian clear cell carcinoma

AbstractLittle is known about the immune environment of ovarian clear cell carcinoma (OCCC) and its impact on various ethnic backgrounds. The aim of this OCCC immune‐related gene expression signatures (irGES) study was to address the interaction between tumour and immune environment of ethnically‐diverse Asian and Caucasian populations and to identify relevant molecular subsets of biological and clinical importance. Our study included 264 women from three different countries (Singapore, Japan, and the UK) and identified four novel immune subtypes (PD1‐high, CTLA4‐high, antigen‐presentation, and pro‐angiogenic subtype) with differentially expressed pathways, and gene ontologies using the NanoString nCounter PanCancer Immune Profiling Panel. The PD1‐high and CTLA4‐high subtypes demonstrated significantly higher PD1, PDL1, and CTLA4 expression, and were associated with poorer clinical outcomes. Mismatch repair (MMR) protein expression, assessed by immunohistochemistry, revealed that about 5% of OCCCs had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4‐high subtype. Our results suggest that OCCC from women of Asian and Caucasian descent shares significant clinical and molecular similarities. To our knowledge, our study is the first study to include both Asian and Caucasian women with OCCC and helps to shine light on the impact of ethnic differences on the immune microenvironment of OCCC. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.