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

Abstract

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.