Neoadjuvant and adjuvant pembrolizumab in advanced high-grade serous carcinoma: the randomized phase II NeoPembrOV clinical trial.

This open-label, non-comparative, 2:1 randomized, phase II trial (NCT03275506) in women with stage IIIC/IV high-grade serous carcinoma (HGSC) for whom upfront complete resection was unachievable assessed whether adding pembrolizumab (200 mg every 3 weeks) to standard-of-care carboplatin plus paclitaxel yielded a complete resection rate (CRR) of at least 50%. Postoperatively patients continued assigned treatment for a maximum of 2 years. Postoperative bevacizumab was optional. The primary endpoint was independently assessed CRR at interval debulking surgery. Secondary endpoints were Completeness of Cytoreduction Index (CCI) and peritoneal cancer index (PCI) scores, objective and best response rates, progression-free survival, overall survival, safety, postoperative morbidity, and pathological complete response. The CRR in 61 pembrolizumab-treated patients was 74% (one-sided 95% CI = 63%), exceeding the prespecified ≥50% threshold and meeting the primary objective. The CRR without pembrolizumab was 70% (one-sided 95% CI = 54%). In the remaining patients CCI scores were ≥3 in 27% of the standard-of-care group and 18% of the investigational group and CC1 in 3% of the investigational group. PCI score decreased by a mean of 9.6 in the standard-of-care group and 10.2 in the investigational group. Objective response rates were 60% and 72%, respectively, and best overall response rates were 83% and 90%, respectively. Progression-free survival was similar with the two regimens (median 20.8 versus 19.4 months in the standard-of-care versus investigational arms, respectively) but overall survival favored pembrolizumab-containing therapy (median 35.3 versus 49.8 months, respectively). The most common grade ≥3 adverse events with pembrolizumab-containing therapy were anemia during neoadjuvant therapy and infection/fever postoperatively. Pembrolizumab was discontinued prematurely because of adverse events in 23% of pembrolizumab-treated patients. Combining pembrolizumab with neoadjuvant chemotherapy is feasible for HGSC considered not completely resectable; observed activity in some subgroups justifies further evaluation to improve understanding of the role of immunotherapy in HGSC.

Real-World Data on Olaparib in Relapsed BRCA-mutated Ovarian Cancer: A Multicenter GINECO RETROLA Cohort Study.

BACKGROUND/AIM: Olaparib was approved in 2014 by the European Medicines Agency (EMA) as maintenance treatment for patients with breast cancer gene (BRCA)-mutated platinum-sensitive relapsed high-grade epithelial ovarian cancer (EOC) following the results of the Study 19. We present the results of a national real-world study on the effectiveness of olaparib in relapsed BRCA-mutated EOC patients. PATIENTS AND METHODS: Patients with EOC, peritoneal, and/or fallopian-tube cancer treated with olaparib in a French Center between May 2014 and March 2017 were included. The primary end-point of the study was progression-free survival. RESULTS: Of the 128 patients analyzed, 89 were treated according to the EMA label. The median progression-free survival was 17.0 months. The most common treatment-related toxicity was fatigue. Treatment-related myelodysplastic syndrome (n=5) and a second cancer (n=1) were diagnosed. CONCLUSION: In this real-life setting, olaparib confirmed its efficacy and safety profile, as previously shown in clinical trials.

Antifungal combination treatment: a future perspective.

The use of antifungal combination therapy is a new clinical approach for combating fungal infections. Although few conclusive clinical studies have been performed to date, data exist that strongly suggest that combination therapy would benefit specific patient subgroups (e.g. stem-cell transplant recipients). This paper examines the evidence available from in vitro, experimental, and clinical studies, and seeks to discover viable clinical strategies for this promising new therapeutic approach.