Olaparib in the therapy of advanced ovarian cancer: first real world experiences in safety and efficacy from China

Abstract

PurposePoly (ADP-ribose) polymerase (PARP) inhibitor, is a milestone in treatment of ovarian cancer. However, there is no real world study from China regarding the clinical outcome of the taking PARP inhibitor (PARPi), Olaparib(Lynparza™). The goal of this research is to evaluate the side effects and short-term efficacy in advanced ovarian cancer patients who administered Olaparib.MethodsPatients with ovarian cancer, fallopian tube cancer and peritoneal cancer that treated with Olaparib in The Affiliated Cancer Hospital of Nanjing Medical University between September 2018 and June 2019 were recruited. The drug associated Adverse Events (AEs) were collected and short-term efficacy were analyzed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) .ResultsOf all 28 enrolled patients, 92.9% were ovarian cancer, 7.1% were fallopian tube cancer, and 39.3% cases harbored germline BRCA-mutation. There were 6(21.4%) patients received Olaparib after multi-line chemotherapy, and 10 patients (35.7%) as second-line maintenance therapy and 2 patients (7.1%) as first-line maintenance therapy. There were still other 10 cases (35.7%) received Olaparib as exploratory therapy. Abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling were newly reported AEs. Serious Adverse Events(SAEs) were usually managed by dose interruption or dose reduction, rather than discontinuation. 3 patients discontinued treatment, 8 patients received reduced dose of Olaparib, and 4 patients stopped therapy after the alleviation of AEs. Of all 28 enrolled cases, in monotherapy group, 1 of 6 patients achieved stable disease(SD) and also 2 patients achieved stable disease(SD) combined with anti-angiogenic drugs when disease progressed. 2 patients achieved complete remission(CR) and 3 patients were stable with exploratory therapy.ConclusionsThe AEs of Olaparib were all manageable. For the first time, we also identified several AEs such as abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling during the follow-up which have not been reported. The short-term efficacy was observed in some exploratory cases that provided new potential indication to PARPi-related clinical trials.

Tumor burden is a potential marker of PARP inhibitor effects in ovarian cancer: a head-to-head observational series

“…Additionally, the present series detected that PARPi as second-line monotherapy were also effective for patients with low tumor loads. Despite the therapeutic effect of olaparib in BRCAwt ovarian cancer with low tumor load, disease progression was found in BRCAmt ovarian cancer with high tumor load in our previous observations and in this study [17]. The better short-term efficacy of the three patients was possibly related to the lower tumor load, which may influence the heterogeneity of tumor cells.…”

Olaparib Outcomes in Patients with BRCA 1-2 Mutated, Platinum-Sensitive, Recurrent Ovarian Cancer in Croatia: A Retrospective Noninterventional Study

“…Percentage of patients whose olaparib dose was reduced to control the adverse events has been very similar across different studies as well, ranging from 14% in Swedish registry real-world study [19], over 21%, 23%, 25%, and 26% in Italian study [14], Study 19 [2], SOLO2 [3], and our study, respectively, to 36% in Korean study [17]. It seems that the incidence of adverse events is somewhat higher in randomized controlled trials (35% and 36% in Study 19 and SOLO2, respectively) than in real-world data studies (17% in our study and 17% in Chinese study [20]). is should probably be explained by the more rigorous documentation and adverse events detection protocols used in randomized controlled trials than in the routine everyday clinical practice.…”

Uptake of Family-Specific Mutation Genetic Testing Among Relatives of Patients with Ovarian Cancer with BRCA1 or BRCA2 Mutation

“…We compared the between the' uptake of FSM testing' and the 'non-uptake of FSM testing' groups. (Table 2) The median surviving family number did not differ significantly between the two groups (median [range]: 8 [3][4][5][6][7][8][9][10][11][12][13][14][15] in the uptake of FSM testing group, 8 [4][5][6][7][8][9][10][11][12][13][14][15][16][17] in the non-uptake of FSM testing group).…”

“…To-date, several studies on the importance of genetic testing in various cancer-related fields have been published [ 16 ]. Meticulous pre-test counseling is important to improve patients’ understanding of disease and increase the number of proband relatives undergoing testing aimed at detecting autosomal dominant cancer syndrome.…”