Search

Background: Maintenance therapy with the poly (ADP-ribose) polymerase inhibitors (PARPis) for platinum-sensitive recurrent ovarian carcinoma (OC) have proven to be effective compared with placebo. We aimed to evaluate the cost-effectiveness (CE) of maintenance fuzuloparib compared to routine surveillance (RS), niraparib and olaparib for platinum-sensitive recurrent OC from the Chinese healthcare systems. Method: A partitioned survival model with three-state (progression-free, progressed, death) was constructed utilizing TreeAge Pro 2011 software to evaluate the economic value of fuzuloparib, niraparib and olaparib maintenance treatment for platinum-sensitive recurrent OC based on the clinical data derived from FZOCUS-2, ENGOT-OV16/NOVA and ENGOT-Ov21/SOLO2. Transition probabilities were estimated from the reported survival probabilities in those trials. Cost and health preference data were derived from the literature. The quality-adjusted life-years (QALYs) and lifetime costs were measured for this analysis. A 5 years horizon and 5%/year discount rates were used. One-way analysis, and probabilistic sensitivity analysis (PSA) were performed to explore the model uncertainties. Results: Total cost of fuzuloparib, niraparib and olaparib were $31628.10, $48183.48 and $54605.54, whereas they had an incremental cost-utility ratio of $31992.69, $32216.08 and $23359.26 per additional progression-free survival (PFS) QALYs gained compared with RS, relatively. Model showed that maintenance fuzuloparib achieved at least an 85.5% probability of CE at the threshold of $37654.50/QALY. One-way sensitivity analysis revealed that the results were sensitive to the PFS and the price of medicines. Conclusion: Fuzuloparib was less cost-effective for patients with germline BRCA1/2 mutation and platinum-sensitive recurrent OC compared to olaparib, but was superior to niraparib from the Chinese healthcare systems perspective. [ABSTRACT FROM AUTHOR]

Objectives: Women with ovarian cancer (OC) have experienced unprecedented challenges since the novel coronavirus disease-2019 (COVID-19) outbreak in China. We aim to evaluate the experience of psychological status, physical symptoms and quality of life (QoL) and investigate the impact of COVID-19 pandemic on OC patients receiving olaparib. Methods: The survey was conducted online from April 22 to May 12 in 2020. Demographic and clinical questions were listed to collect general information. The degree of insomnia, depression, anxiety, stress symptoms and QoL were assessed by the Chinese versions of the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the General Functional Assessment of Cancer Therapy, respectively. Multivariate logistic regression analysis was conducted to analyze the risk factors for mental distress and QoL. Results: A total of 56 respondents coming from 15 various provinces in China participated in the survey. The prevalence of insomnia, depressive, anxiety, stress symptoms and reduced QoL were 37.5, 51.8, 37.5, 30.4, and 51.8%, respectively. Unfavorable disease status, shorter period of olaparib administration, adverse events of olaparib and delay in cancer care were correlated with mental health problems. Reduced QoL was also significantly associated with psychological distress. Conclusions: This study emphasized that mental health problems and reduced QoL should gain more attention in women with OC who are receiving oral olaparib at home. Appropriate psychological healthcare strategies are necessary for OC patients during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the real-world application, effectiveness, and safety of olaparib and niraparib as maintenance therapies in patients with platinum-sensitive recurrent ovarian cancer (PSROC) in China and investigated clinical factors associated with prolonged benefits of poly ADPribose polymerase (PARP) inhibitors to help guide clinician treatment-decision making in daily practice. Methods: This real-world single-center retrospective cohort study was conducted at the Shandong Cancer Hospital and Institute. Archival data of consecutive patients diagnosed with PSROC who achieved a complete response (CR) or partial response (PR) after the last platinum-based chemotherapy and treated with olaparib or niraparib as maintenance therapy from August 2018 to September 2021 were collected. Results: Overall, 106 women were included in the cohort. Seventy-two (68%) patients were treated with olaparib, while 34 (32%) received niraparib; 99.1% of the patients were diagnosed with high-grade serous carcinoma, and 73.6% had FIGO stages III-IV. Approximately 71.7% of the patients had received PARP inhibitors after the second platinum-based line and 44.3% of the patients achieved a CR in their last platinum-based therapy. The median platinumfree interval (PFI) after the penultimate platinum-based therapy was 10 (95% CI: 10-13.6) months. The median PFS was 21 (95% CI: 13-24.5) months and the median CFI was 22 (95% CI: 16-26.5) months. Consistent with the univariate analysis, the multivariate analysis identified three independent factors associated with prolonged progression-free survival (PFS) and chemotherapy-free interval (CFI): breast cancer susceptibility gene (BRCA) mutant type (p = 0.005 and p = 0.003); PFI =12 months (p = 0.01 and p = 0.006); and CR to last platinum-based therapy (p = 0.016 and p = 0.019). It was found that there was no appreciable difference in any grade 3-4 hematological AE between patients who received olaparib and niraparib. Conclusion: Maintenance treatment with olaparib and niraparib is effective and well tolerated for PSROC patients in real-world clinical practice. Three clinical factors were identified that predicted prolonged survival under maintenance therapy with PARP inhibitors: BRCA mutant type, PFI =12 months, and CR to last platinum-based therapy. These findings should be further confirmed with an appropriately powered analysis in studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the cost-effectiveness of olaparib as the maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation in China. Methods: A Markov model was developed to simulate the clinical course of typical patients with ovarian cancer in the SOLO2 trial. The Weibull survival model was employed to fit the Kaplan-Meier progression-free survival and overall survival probabilities of the olaparib and placebo strategies, respectively. The clinical and direct costs data were derived from randomized clinical trials and published reports. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated over a 10-year lifetime horizon. Meanwhile, one-way and probabilistic sensitivity analyses were used to explore the impact of uncertainty on the model's outcomes. Results: Overall, the incremental effectiveness and cost of olaparib versus placebo were 0.56 QALYs and $43,292.92, respectively, resulting in an ICER of $77,620.56/QALY, higher than the willingness-to-pay (WTP) threshold of China ($31,498.70/QALY). The results were sensitive to the cost of olaparib and utility of PFS. Scenario analyses suggested that when the cost of olaparib was reduced by 60%, ICER decreased to $30,611.52/QALY, lower than the WTP threshold of China. Conclusion: The findings from the present analysis suggest that olaparib with a 60% discount as maintenance therapy might be cost effective in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation in China. [ABSTRACT FROM AUTHOR]

Olaparib was the first poly ADP-ribose polymerase inhibitor approved for patients with cancer with mutations in either BRCA1 or BRCA2 in China. To the best of our knowledge, however, no study has described the efficacy of olaparib for patients with breast cancer with double mutations in BRCA1 and BRCA2. The present case report describes a patient with breast cancer with deleterious germline mutations in both BRCA1 and BRCA2. The 56-year-old patient with multiple metastatic breast cancer underwent breast cancer resection with 12 years interval between removal of the left and right breast. Germline mutations in both BRCA1 (S405X) and BRCA2 (W2990X) were identified by NGS. She received two cycles of chemotherapy with a combination of albumin-bound paclitaxel and capecitabine; the response was progressive disease. Subsequently, the patient was treated with a gradual dosage of decreasing olaparib (600 to 300 mg BID) for 6 months until grade 3 anemia could not be alleviated by giving erythropoietin and iron, and CT imaging showed a partial response (35% reduction). The patient then switched to exemestane therapy due to the continuous grade 3 anemia. In conclusion, the present study reported a female patient with double heterozygosity of BRCA1 and BRCA2 who benefited from olaparib monotherapy. Thus, olaparib may be a suitable treatment for such patients. [ABSTRACT FROM AUTHOR]

Maintenance therapy with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib provided a substantial progression-free survival (PFS) benefit compared with placebo in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (BRCAm) who were in clinical complete or partial response following platinum-based chemotherapy in the Phase III SOLO1 global study. This led to the approval of maintenance olaparib in China, USA, EU, Japan and other countries, in the newly diagnosed setting. This separate China cohort of the SOLO1 study investigated the efficacy and safety of maintenance olaparib within the Chinese population. In this double-blind, multicentre study, patients were randomized 2:1 to receive oral olaparib tablets (300 mg twice daily) or placebo. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Of the 64 randomized patients, 44 received olaparib and 20 placebo. Olaparib reduced the risk of disease progression or death by 54% compared with placebo (HR 0.46, 95% Cl 0.23–0.97; median PFS was not reached in the olaparib arm vs 9.3 months in the placebo arm). The most common AEs in the olaparib arm were nausea (63.6 vs 25.0% with placebo), anaemia (59.1 vs 15.0%) and leukopenia (54.5 vs 20.0%). Grade ≥3 AEs were experienced by 56.8% of olaparib patients and 30.0% of placebo patients. Results in the SOLO1 China cohort support the use of olaparib as maintenance treatment for Chinese patients with newly diagnosed advanced ovarian cancer who have a BRCAm and are in complete or partial response after platinum-based chemotherapy. • Maintenance treatment with olaparib provides a clinically relevant progression-free survival in Chinese patients • Safety and tolerability findings are consistent with those reported in other olaparib studies • Supports use of olaparib as maintenance therapy in Chinese patients with newly diagnosed advanced ovarian cancer and BRCAm [ABSTRACT FROM AUTHOR]

Objectives: Results of the SOLO1 study (Moore et al. N Engl J Med 2018) led to the approval of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in the USA, the EU, Japan, and China as maintenance treatment in patients with a BRCA1 and/or BRCA2 mutation (BRCAm) following response to first-line (1L) platinum-based chemotherapy (PBC). Maintenance PARP inhibitor, with or without bevacizumab, has been shown to provide benefit to patients with newly diagnosed advanced ovarian cancer (OC) without a BRCAm (González-Martin et al. N Engl J Med 2019; Ray-Coquard et al. N Engl J Med 2019). The MONO-OLA1 study (NCT04884360) assesses the efficacy and safety of olaparib maintenance monotherapy when compared with placebo in patients with BRCA wild-type (BRCAwt) advanced OC following response to 1L PBC. Methods: MONO-OLA1 is a Phase III, randomized, double-blind, placebo-controlled, international study. Eligible patients must have higher risk newly diagnosed BRCA wt advanced OC (FIGO stage III/IV) and have a complete response (CR) or partial response (PR) following 1L PBC. Patients with stage III disease who have complete cytoreduction following primary debulking surgery are not eligible. Patients will be randomly assigned (2:1 target, n =420) to receive either olaparib (300 mg bid) or placebo tablets. Randomization will be stratified by response to 1L PBC (CR and PR), homologous recombination deficiency (HRD) status (positive and negative/unknown), and region (China and other international sites). The number of patients with HRD-negative/unknown status will be capped at approximately 60% of the total patient population. The primary endpoints are investigator-assessed progression-free survival (PFS) by RECIST v1.1 in the BRCA wt HRD-positive and BRCA wt groups. A PFS sensitivity analysis by blinded independent central review will be performed to confirm the primary efficacy findings. The key secondary endpoints are second progression-free survival, overall survival, and safety and tolerability. Other secondary endpoints include time to first subsequent therapy or death, time to second subsequent therapy or death, and health-related quality of life. Exploratory endpoints include translational analyses to identify predictive biomarkers of response to olaparib. Enrollment began in May 2021. [ABSTRACT FROM AUTHOR]

Objectives: Maintenance therapy with the PARP inhibitor olaparib (with or without the antiangiogenic agent bevacizumab) leads to significant progression-free survival (PFS) benefits in patients with newly diagnosed advanced ovarian cancer (OC) (with or without a BRCA' and/or BRCA2 mutation [ BRCA m]) (Moore et al. N Eng J Med 2018; Ray-Coquard et al. N Eng J Med 2019). Preclinical data have shown a potential synergistic antitumor effect when combining an immune checkpoint inhibitor with an antiangiogenic agent and a PARP inhibitor. The combination has shown promise as a treatment in platinum-sensitive relapsed non-germline BRCA m OC patients (Drew et al. ESMO 2020). The Phase III DUO-O trial (NCT03737643) began global enrollment in January 2019 and will evaluate the efficacy and safety of combinations of the standard of care platinumbased chemotherapy, bevacizumab, and the anti-PD-L1 antibody durvalumab, followed by maintenance bevacizumab, durvalumab, and olaparib in patients with newly diagnosed advanced OC (Harter et al. ASCO 2019). The China cohort will evaluate these combinations in a standalone analysis of patients with non- BRCA m tumors. Methods: Eligible patients must have newly diagnosed stage III or IV high-grade ovarian, epithelial, fallopian, or primary peritoneal cancer and have undergone upfront primary surgery or be planned to have interval debulking surgery. From sites in China, ~120 patients with a non- BRCA m tumor (using a China-based central laboratory to determine BRCA m status) will be randomized 1:1:1 to: chemotherapy + bevacizumab + durvalumab, followed by bevacizumab + durvalumab + olaparib maintenance; chemotherapy + bevacizumab + durvalumab, followed by bevacizumab + durvalumab + placebo maintenance; or chemotherapy + bevacizumab + placebo, followed by bevacizumab + placebo. Olaparib (300 mg bid) and durvalumab (1120 mg q3w) will be administered for up to 24 months, and bevacizumab (15 mg/kg q3w) for up to 15 months, or until disease progression. The primary endpoints are investigator-assessed PFS (modified RECIST v1.1) in all patients with a non- BRCA tumor and patients with a non- BRCA , homologous recombination deficiency-positive tumor. A key secondary efficacy endpoint is overall survival, and safety will be summarized descriptively. Local China protocol amendments are in progress, and relevant updates will be presented. Enrollment in China began in April 2021. [ABSTRACT FROM AUTHOR]

To evaluate the real-world effectiveness and gene predictive analysis of olaparib in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC), a multicenter, retrospective, real-world study was conducted by involving Chinese patients with mCRPC from December 2017 to June 2021. Homologous Recombination repair (HRR)gene mutation (HRRm) status was identified using targeted next-generation sequencing (NGS). The primary end point includes prostate-specific antigen (PSA) response rate (PSA 50 ). Secondary end points include PSA progression-free survival (PSA-PFS), exploratory endpoints include PSA 50 , and PSA-PFS in HRRm-negative patients with variants of unknown significance (VUS). Survival rates were analyzed using Kaplan-Meier (KM) plot. A total of 39 eligible patients with a median age of 65 (interquartile range [IQR]: 59.5-69.5) years were included in the study. Overall, 40% (12/30) of the patients with mCRPC achieved PSA 50 and the median PSA-PFS was 3.1 months (95% Confidence interval [CI]: 2.4-7). Furthermore, higher PSA 50 rate and longer PSA-PFS were observed in HRRm-positive patients (PSA 50 : 50% [7/14]; median PSA-PFS: 5.3 months, 95% CI: 3.73-10). Among the HRRm-positive patients, those harboring the BRCA2 aberrations experienced best clinical efficacy (PSA 50 : 55.5% [5/9] and median PSA-PFS [95% CI]: 9.5 months [4.3, NA]). Clinical benefit was also observed in HRRm-negative patients (PSA50: 31.3% [5/16]; median PSA-PFS [95% CI]:2.05 months [1.5,8]), wherein most patients with a PSA 50 response were carrying VUS (PSA 50 : 50% [4/8]; median PSA-PFS [95% CI]: 2.75 months [1.27, NA]). In one patients with mutation in the ATR gene, the PSA level decreased by 62%. Olaparib improved PSA response and prolonged PSA-PFS in Chinese mCRPC patients especially in those carrying HRR mutation. Among the HRR genes, patients with BRCA2 mutation showed the best clinical benefit. Besides, some patients carrying VUS on HRR gene and other DNA damage response (DDR) gene mutations also showed response to olaparib treatment, indicating that the clinical benefits observed in HRR-negative group were driven by VUS and other DDR gene mutation. However, this should be further explored in the future, and more molecular functional studies are needed to reclassify VUS for better clinical treatment decision-making and management of mCRPC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The PARP inhibitor olaparib has been shown to have clinical efficacy in patients with a germline BRCA mutation and ovarian or breast cancer. However, the high treatment cost associated with this drug limits its viability as a clinical treatment option. This work aims to evaluate the cost-effectiveness of olaparib as a maintenance treatment for metastatic pancreatic cancer from the perspective of the United States and China healthcare systems and provides valuable suggestions for clinical decision making. Method: A three-state Markov model (progression-free, progressed disease, death) was constructed using TreeAge Pro 2020 software to evaluate the economic value of olaparib vs. placebo maintenance treatment for metastatic pancreatic cancer based on the clinical data derived from phase III randomized controlled trial (POLO, ClinicalTrials.gov number, NCT02184195). Total costs, quality-adjusted life years and incremental cost-effectiveness ratio were used as economic indicators for this analysis. A 5-years horizon and 5%/year discount rates were used. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to assess the model uncertainty. Results: The incremental cost-effectiveness ratios (ICERs) of the use of olaparib vs. placebo in China and the United States were $6,694/QALY and $13327/QALY, respectively. All ICERs were far below the thresholds of $30829 in China and $50000 in the United States. Sensitivity analysis confirmed a stable economic advantage in the use of olaparib vs. placebo as maintenance therapy in China and the United States. Conclusion: Olaparib was estimated to be more cost effective than placebo for the maintenance therapy of patients with a germline BRCA mutation and pancreatic cancer in China and the United States at thresholds of $30829 and $50000 per QALY, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Poly (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. Methods: Patients 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). Results: Of 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. Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Purpose: Chinese patients have been enrolled in multiple Phase III trials of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza); however, the pharmacokinetic (PK) profile of olaparib has not been investigated in this population. This two-part, open-label Phase I study was, therefore, carried out to determine the PK and safety profile of olaparib (tablet formulation) in Chinese patients with advanced solid tumours as monotherapy and in combination with paclitaxel (NCT02430311)., Methods: The PK profile of olaparib 300 mg (twice daily [bid]; Cohort 1) as monotherapy after a single dose and at steady state, and 100 mg (bid; Cohort 2) as monotherapy (single dose and at steady state) and in combination (at steady state) with weekly paclitaxel (80 mg/m 2 ) was assessed during Part A. Patients could continue to receive treatment (monotherapy, Cohort 1; combination therapy, Cohort 2) in Part B, which assessed safety and tolerability., Results: Twenty and 16 patients were enrolled into Cohorts 1 and 2, respectively. Steady-state olaparib exposure increased slightly less than proportionally with increasing monotherapy dose and inter-patient variability was high. A statistically significant decrease in olaparib exposure was seen when given in combination with paclitaxel. Discontinuation due to adverse events (AEs) was rare and haematological AEs were more common in patients receiving combination treatment., Conclusions: The PK and safety profile of olaparib monotherapy in Chinese patients is consistent with that seen previously in Western and Japanese patients, and the recommended Phase III monotherapy tablet dose (300 mg bid) is suitable for use in this population.