Real-world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau.
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ABSTRACT: Background
Olaparib has been approved as an active and maintenance therapy for patients with platinum-sensitive, BRCA-mutated high-grade serous ovarian cancer (SOC). However, the efficacy and safety data is lack among Chinese ovarian cancer patients.Aim
This real-world study aimed to evaluate the effectiveness and safety profile of olaparib in patients from mainland China, where olaparib is currently unavailable.Methods and results
This single-center, observational study included 65 patients with pathologically confirmed advanced serous ovarian cancer from Kiang Wu Hospital in Macau between December 2015 and September 2017. Progression-free survival (PFS) and other endpoints (treatment response, disease progression, and adverse events) were evaluated. PFS was estimated using the Kaplan-Meier method. The median treatment duration was 4 months (range, 1-15). The median PFS for the overall population was 4.2 months (95% CI 2.7-5.2), while those for patients with wild-type BRCA1/2 and BRCA1/2 mutations were 3.1 months (95% CI 1.3-4.6) and 5.3 months (95% CI 2.8-7.1), respectively. The median PFS tended to be longer for patients on maintenance therapy (between 9.0 months [95% CI 1.4-17.5] and 10.0 months [95% CI 2.5-18.1]) than for those on active therapy (between 3.1 months [95% CI 2.1-3.8] and 3.0 months [95% CI 1.4-4.5]). Most patients (87.0%) experienced low-grade adverse events; the most common of which were fatigue (49.0%) and nausea (35.0%).Conclusion
Our findings demonstrate clinical benefit of olaparib to mainland Chinese patients with high-grade SOC, particularly for patients with BRCA mutations and who require maintenance therapy.
SUBMITTER: Cao Y
PROVIDER: S-EPMC7941423 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Olaparib maintenance therapy has shown efficacy and tolerability in patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). Our aim was to present real-world experience with olaparib in Korea. METHOD:We included HSROC patients with BRCAm treated with olaparib maintenance at four institutions in Korea between 2016 and 2018. Medical records were reviewed for clinico-pathologic characteristics, objective response, survival outcomes, and safety. RESULTS:One hundred HSROC patients with BRCAm were included. BRCA1 mutation was present in 71 patients (71.0%), and BRCA2 mutation was present in 23 patients (23.0%). In terms of the best objective response with olaparib maintenance in 53 patients with partial remission from most recent chemotherapy, complete remission occurred in 12 (22.6%) and partial remission in four (7.5%), while 33 patients (62.3%) had stable disease. The 24 month progression-free survival was 42.4%, and 24 month overall survival was 82.1%. Grade 3 or more adverse events were as follows: anemia in 14 patients (14.0%), neutropenia in seven patients (7.0%), thrombocytopenia in two patients (2.0%), oral mucositis in one patient (1.0%), and soft tissue infection in one patient (1.0%). CONCLUSIONS:The safety and effectiveness of olaparib maintenance treatment in a real-world study were consistent with those reported in previous clinical trials.
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Project description:IntroductionMuch drug development and published analysis for epithelial ovarian cancer (EOC) focuses on early-line treatment. Full sequences of treatment from diagnosis to death and the impact of later lines of therapy are rarely studied. We describe the establishment of an international network of cancer centers configured to compare real-world treatment pathways in UK, Portugal, Germany, South Korea, France and Romania (the Ovarian Real-World International Consortium; ORWIC).Methods3344 patients diagnosed with EOC (2012-2018) were analysed using a common data model and hub and spoke programming approach applied to existing electronic medical records. Consistent definition of line of therapy between sites and an efficient approach to analysis within the limitations of local information governance was achieved.ResultsMedian age of participants was 53-67 years old and 5-29% were ECOG >1. Between 62% and 84% of patients were diagnosed with late-stage disease (FIGO III-IV). Sites treating younger and fitter patients had higher rates of debulking surgery for those diagnosed at late stage than sites with older, more frail patients. At least 21% of patients treated with systemic anti-cancer therapy (SACT) had recurrent disease following second-line therapy (2L); up to 11 lines of SACT treatment were recorded for some patients. Platinum-based SACT was consistently used across sites at 1L, but choices at 2L varied, with hormone therapies commonly used in the UK and Portugal. The use (and type) of maintenance therapy following 1L also varied. Beyond 2L, there was little consensus between sites on treatment choice: trial compounds and unspecified combinations of other agents were common.DiscussionSpecific treatment sequences are reported up to 4L and the establishment of this network facilitates future analysis of comparative outcomes per line of treatment with the aim of optimizing available options for patients with recurrent EOC. In particular, this real-world network can be used to assess the growing use of PARP inhibitors. The real-world optimization of advanced line treatment will be especially important for patients not usually eligible for involvement with clinical trials. The resources to enable this analysis to be implemented elsewhere are supplied and the network will seek to grow in coverage of further sites.
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Project description:Immune checkpoint and MAP kinase pathway inhibitors can significantly improve long-term survival for patients with melanoma. There is limited real-world data of these regimens' effectiveness. We retrospectively analyzed 402 patients with unresectable and metastatic melanoma between August 2013 and July 2020 treated with immune checkpoint inhibitors and MAP kinase pathway targeted therapy in Alberta, Canada. Overall survival (OS) was compared using Kaplan-Meier and Cox regression analyses. Subgroup survival outcomes were analyzed by first-line treatment regime and BRAF mutation status. Three treatment eras were defined based on drug access: prior to August 2013, August 2013 to November 2016, and November 2016 to July 2020. Across each era, there were improvements in median OS: 11.7 months, 15.9 months, and 33.6 months, respectively. Patients with BRAF mutant melanoma had improved median OS when they were treated with immunotherapy in the first line as opposed to targeted therapy (median OS not reached for immunotherapy versus 17.4 months with targeted treatment). Patients with BRAF wild-type melanomas had improved survival with ipilimumab and nivolumab versus those treated with a single-agent PD-1 inhibitor (median OS not reached and 21.2 months). Our real-world analysis confirms significant survival improvements with each subsequent introduction of novel therapies for advanced melanoma.
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Project description:BackgroundDetailed epidemiologic descriptions of large populations of advanced stage ovarian cancer patients have been lacking to date. This study aimed to describe the patient characteristics, treatment patterns, survival, and incidence rates of health outcomes of interest (HOI) in a large cohort of advanced stage ovarian cancer patients in the United States (US).MethodsThis cohort study identified incident advanced stage (III/IV) ovarian cancer patients in the US diagnosed from 2010 to 2018 in the HealthCore Integrated Research Database (HIRD) using a validated predictive model algorithm. Descriptive characteristics were presented overall and by treatment line. The incidence rates and 95% confidence intervals for pre-specified HOIs were evaluated after advanced stage diagnosis. Overall survival, time to treatment discontinuation or death (TTD), and time to next treatment or death (TTNT) were defined using treatment information in claims and linkage with the National Death Index.ResultsWe identified 12,659 patients with incident advanced stage ovarian cancer during the study period. Most patients undergoing treatment received platinum agents (75%) and/or taxanes (70%). The most common HOIs (> 24 per 100 person-years) included abdominal pain, nausea and vomiting, anemia, and serious infections. The median overall survival from diagnosis was 4.5 years, while approximately half of the treated cohort had a first-line time to treatment discontinuation or death (TTD) within the first 4 months, and a time to next treatment or death (TTNT) from first to second-line of about 6 months.ConclusionsThis study describes commercially insured US patients with advanced stage ovarian cancer from 2010 to 2018, and observed diverse treatment patterns, incidence of numerous HOIs, and limited survival in this population.
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Project description:BackgroundTalazoparib is a poly (adenosine diphosphate-ribose) polymerase inhibitor approved for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative, locally advanced or metastatic breast cancer (LA/mBC), with approval based on the EMBRACA trial. To date, there are no published data on talazoparib use in the real-world United States (USA) setting.Patients and methodsCharacteristics, treatment patterns, and clinical outcomes of real-world US patients with gBRCAm HER2-negative LA/mBC treated with talazoparib monotherapy were collected via retrospective chart review and summarized using descriptive statistics.ResultsAmong 84 eligible patients, 35.7% had hormone receptor-positive tumors and 64.3% had triple-negative LA/mBC (TNBC). At talazoparib initiation, 29.8% had ECOG PS of ≥2 and 19.0% had brain metastasis. Mutations in gBRCA1 or 2 were detected among 64.3% and 35.7% of patients, respectively. Talazoparib was given as 1st-line therapy in 14.3% of patients, 2nd-line in 40.5%, and 3rd- or 4th-line in 45.2%. Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9), the median time from initiation to chemotherapy was 12.2 months (95% CI, 10.5-20.1), and the overall response rate was 63.1%. No differences in clinical outcomes were observed between patients with HR-positive/HER2-negative LA/mBC and patients with TNBC by using unadjusted statistical comparisons. Brain metastasis and ECOG PS ≥2 at talazoparib initiation were associated with treatment failure and progression or mortality.ConclusionOverall, talazoparib clinical outcomes in this real-world population are consistent with findings from EMBRACA.
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Project description:Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019.MethodsInformation of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR).ResultsDaratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001).ConclusionThe real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.
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Project description:Background:Advanced breast cancer (abc) represents a substantial burden for patients and caregivers. In the present study, we aimed to estimate quality of life (qol), utility, productivity loss, pain, health care resource utilization, and costs for patients with abc, and qol, utility, and productivity loss for their caregivers. Methods:This multicentre prospective non-interventional study was conducted in Canada. Eligible participants were postmenopausal women with estrogen receptor-positive, her2-negative unresectable abc and their caregivers. Validated questionnaires were used to measure qol, utility, productivity loss, and pain. Patients and caregivers were classified into 4 health states typically used in oncology economic modelling: first-line progression-free (1l-pf), first-line progressive disease (1l-pd), second- or subsequent-line progression-free (?2l-pf), and second- or subsequent-line progressive disease (?2l-pd). Results:Most patients and caregivers accepted to participate, with total recruitment of 202 patients and 78 caregivers. Compared with patients in pf, patients in pd had lower mean qol scores (52.9 ± 29.9 for 1l-pd vs. 68.2 ± 23.2 for 1l-pf, and 54.0 ± 23.6 for ?2l-pd vs. 66.0 ± 22.1 for ?2l-pf), lower mean utility values (0.64 ± 0.22 for 1l-pd vs. 0.73 ± 0.20 for 1l-pf, and 0.65 ± 0.25 for ?2l-pd vs. 0.74 ± 0.18 for ?2l-pf), and greater productivity loss (39.4 ± 27.7 for 1l-pd vs. 27.5 ± 30.1 for 1l-pf, and 37.6 ± 29.2 for ?2l-pd vs. 32.0 ± 29.0 for ?2l-pf). Compared with caregivers of patients in pf, caregivers of patients in pd had lower qol scores and utility values, and greater productivity loss. Conclusions:Study results indicate that, for patients and caregivers, pd health states are associated with a deterioration of qol and utility and a decrease in productivity in both 1l and ?2l.
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