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Precision medicine based on cancer genomics is being applied in clinical practice. However, patients do not always derive benefits from genomic testing. Here, we performed targeted amplicon exome sequencing‐based panel tests, including 160 cancer‐related genes (PleSSision‐160), on 88 malignant ovarian tumors (high‐grade serous carcinoma, 27; endometrioid carcinoma, 15; clear cell carcinoma, 30; mucinous carcinoma, 6; undifferentiated carcinoma, 4; and others, 6 (immature teratoma, 1; carcinosarcoma, 3; squamous cell carcinoma, 1; and mixed, 1)), to assess treatment strategies and useful biomarkers for malignant ovarian tumors. Overall, actionable gene variants were found in 90.9%, and druggable gene variants were found in 40.9% of the cases. Actionable BRCA1 and BRCA2 variants were found in 4.5% of each of the cases. ERBB2 amplification was found in 33.3% of mucinous carcinoma cases. Druggable hypermutation/ultramutation (tumor mutation burden ≥ 10 SNVs/Mbp) was found in 7.4% of high‐grade serous carcinoma, 46.7% of endometrioid carcinoma, 10% of clear cell carcinoma, 0% of mucinous carcinoma, 25% of undifferentiated carcinoma, and 33.3% of the other cancer cases. Copy number alterations were significantly higher in high‐grade serous carcinoma (P <.005) than in other histologic subtypes; some clear cell carcinoma showed high copy number alterations that were correlated with advanced stage (P <.05) and worse survival (P <.01). A high count of copy number alteration was associated with worse survival in all malignant ovarian tumors (P <.05). Our study shows that targeted agents can be detected in approximately 40% of malignant ovarian tumors via multigene panel testing, and copy number alteration count can be a useful marker to help assess risks in malignant ovarian tumor patients. [ABSTRACT FROM AUTHOR]

Background: Olaparib maintenance therapy for platinum-sensitive relapsed ovarian cancer has been approved in Japan since April 2018. Here, we report the experience administering this therapy in our hospital, with the aim of evaluating efficacy and safety in the Japanese population. Methods: The study included 52 patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer. All patients started olaparib at a dose of 300 mg twice daily. Information about treatment efficacy and adverse effects was collected retrospectively from medical records. Results: Median age was 58 years old (range: 33–80), and 82.7% of the patients were diagnosed with high-grade serous carcinoma. Sixteen patients (30.8%) possessed the BRCA1/2 pathogenic variant (15 germline and 1 tissue), 3 (5.8%) possessed variants of unknown significance (2 germline and 1 tissue), 16 (30.8%) possessed wild type, and 17 (32.7%) were not analyzed. Median progression-free survival was 15.3 months (95% CI 9.0–21.6). Patients with BRCA1/2 pathogenic variants showed significantly longer PFS than patients with wild-type BRCA1/2 (p = 0.007). Disease progression caused 34 cases to discontinue olaparib. Eighteen (34.6%) individuals exhibited ≥ grade 3 anemia, although they recovered in response to appropriate management. One patient discontinued olaparib because of prolonged renal dysfunction. Another patient presented with grade 3 fatigue, but recovered after 2 weeks of interruption and continued olaparib treatment. Conclusion: Olaparib maintenance therapy for platinum-sensitive recurrent ovarian cancer in the Japanese population is sufficiently safe and no less effective than reports from previous studies. [ABSTRACT FROM AUTHOR]

ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer. We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases. ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p < 0.001) or CD8 levels (p < 0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p < 0.001) and HGSC (p < 0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006). ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC. • ARID1A mutation was identified in 41.5 and 45.0% of clear cell and endometrioid ovarian cancer patients, respectively. • ARID1A mutation/ARID1A loss is associated with positive PD-L1 or CD8 levels in clear cell ovarian cancer. • ARID1A mutation is associated with a high tumor mutation burden in clear cell ovarian cancer. [ABSTRACT FROM AUTHOR]