Olaparib as maintenance treatment in relapsed platinum-sensitive BRCA mutated ovarian cancer: real world experience in two Italian cancer Centers

Background: In 2014, after FDA approval, the therapeutic armamentarium of relapsed platinum-sensitive (RPS) ovarian cancer has been enriched by the introduction of a new drug, belonging to the class of poly (ADP-ribose) polymerase inhibitors (PARPi), olaparib. This oral PARPi demonstrated to significantly prolong progression-free survival (PFS) compared to placebo as maintenance in patients with platinum-sensitive recurrent (PSR) BRCA mutated serous ovarian cancer in the pivotal phase II trial. Olaparib is actually used in daily practice, but very few data are available about its safety and activity out of clinical trials. The aim of this paper is to describe the early data on this agent according to its approval in two clinical cancer care Institutions in Italy. Materials and Methods: This is an observational, retrospective study, carried out in two Italian Hospitals (National Cancer Institute of Naples and National Cancer Institute of Milan). Archival medical records of all the BRCA mutated relapsed ovarian cancer patients treated with olaparib in two Italian centers from September 1st, 2015 to March 14th, 2017 were analyzed. The primary endpoint is to describe the percentage of patients that received olaparib for ≥6 months and ≥12 months. Secondary endpoints include: the description of objective response rate (ORR), disease control rate (DCR), PFS and safety profile of olaparib treatment. Olaparib 400 mg twice daily capsules was given orally according to indication. Results: From September 1st, 2015 to March 14th, 2017 twenty-two patients with RPS ovarian cancer were considered eligible for the analysis. At the time of data cut off point, about 55% of patients were receiving olaparib for at least 6 months, and 27.2% for 12 or more months. Actually, most of the patients (77.3%) is still on treatment with the PARPi. Only 3 progressions of disease (PD) were registered, therefore the median PFS has not been reached. The ORR was 33.4% and the DCR was 75%. Olaparib was globally manageable and well tolerated. Safety data were consistent with previously reported findings in literature. Most common adverse events were: fatigue (63.3%); nausea (77.3%); anemia (54.5%); thrombocytopenia (18.1%); leucopenia (36.4%). All the events were mainly of grade 1 and were transient and managed with supportive care. Conclusions: Our preliminary analysis suggests a good benefit/toxicity ratio of olaparib also in unselected population out of clinical trials. The need to evaluate the reproducibility of literature findings in heterogeneous patients require further studies

The role of immunotherapy treatment in non-clear cell renal cell carcinoma: An analysis of the literature

Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group representing 15-30% of renal tumors. They are mostly excluded from immunotherapy trials due to their rarity and worse prognosis. This, alongside nccRCC misdiagnosis/misclassification, lack of immune-biomarker expression rate data, lack of homogeneous data reporting, the retrospective nature of many studies, small sample sizes, and the fact that high-grade evidence only stems from trials mostly addressing the clear cell subtype, result in poorly defined treatments. We thus reviewed available data from several clinical trials, retrospective studies, and meta-analyses on immunotherapy responses and their correlation with histological subtypes and prognostic biomarkers. The papillary and unclassified subtypes are the best candidate for immunotherapy, showing response rates up to similar to 35%. Chromophobe cancers, on the other end, have mostly null response rates. Cancers with sarcomatoid features respond very well to immunotherapy, regardless of their histology. Available data for translocation, medullary, collecting duct, and other nccRCCs are inconclusive. Regarding PD-L1, its expression correlates with better responses, but its prognostic value remains to be determined due to small sample sizes hindering direct statistical comparisons. It is necessary to involve a larger number of nccRCC patients and centers in clinical trials and report tumor response rates and PD-(L)1 and other markers' expression rates divided by nccRCC subtypes and not just for the whole cohorts. This will allow us to collect more robust data to best identify patients who can benefit from immunotherapy and ultimately define the standard of treatment

Triple-Negative Breast Cancers: Systematic Review of the Literature on Molecular and Clinical Features with a Focus on Treatment with Innovative Drugs

Triple-negative breast cancer (TNBC) accounts for 15-20% of diagnosed breast tumours, with higher incidence in young and African-American women, and it is frequently associated with BRCA germline mutations. Chemotherapy is the only well-established therapeutic option in both early- and advanced-stages of the disease. TNBC tumours relapse earlier after standard anthracycline- and/or taxane-based chemotherapy treatments, generally within 1-3 years after the diagnosis, and often develop visceral metastases, representing the subtype with a worse prognosis among all breast cancers. In the present review, we will provide an updated overview of the available results of recent clinical trials for this disease and we will describe the implications of the known molecular pathways representing novel targets for development of future therapies for TNBC patients

Clinical management of advanced gastric cancer: the role of new molecular drugs

Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual "scenario" of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice. (C) 2014 Baishideng Publishing Group Inc. All rights reserved