Objective: Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. Methods: This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). Results: Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. Conclusion This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.

BACKGROUNDS/AIMS: The prognosis of cirrhotic patients with hepatocellular carcinoma (HCC) depends on both residual liver function and tumor characteristics. The aims of this study was to construct a new prognostic index for HCC patients: the modified CLIP score, and to compare its discriminatory ability and predictive power with those of the CLIP score that is currently the most commonly used integrated staging score in patients of HCC. METHODS: A retrospective analysis of 237 cases of HCC diagnosed at Dong-A university hospital was performed. Prognostic analysis was performed for single variables by estimating survival distributions with the Kaplan-Meier's method, and statistically compared by the log-rank test. RESULTS: Patients had a mean age of 57.5 years and were predominantly males (79.7%). The overall median survival period was 25.7 months. It was correlated to ascites, portal vein thrombosis, AFP, tumor size, and Child-Pugh classification. The median survival period was 41.0, 25.2, 13.8, 13.4, and 6.5 months for CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001), and 42.1, 34.0, 25.7, 14.0, and 6.8 months for modified CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001). The Kaplan-Meier's curve showed that the modified CLIP score had additional explanatory power above that of the CLIP score. CONCLUSIONS: The modified CLIP score, compared with the CLIP score, particularly in the score 2- to 3- patient groups of HCC, had greater discriminant ability and survival predictive power, but was not able to discriminate 4- to 6- patient group.
alpha-Fetoproteins/analysis ; Venous Thrombosis/complications ; Survival Analysis ; Prognosis ; Neoplasm Staging ; Middle Aged ; Male ; Liver Neoplasms/complications/mortality/*pathology ; Liver Cirrhosis/complications ; Humans ; Female ; Carcinoma, Hepatocellular/complications/mortality/*pathology ; Aged, 80 and over ; Aged ; Adult