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:BackgroundThis work set out to examine the hematological adverse events (AEs) of an individualized starting dose (ISD) of niraparib in Chinese patients with ovarian cancer (OC).MethodsThe medical records of 43 patients with OC who were treated with an ISD of niraparib at the Cancer Hospital of The University of Chinese Academy of Sciences between February 2019 and January 2020 were retrospectively reviewed. Treatment-emergent hematological AEs were analyzed.ResultsOf the 43 patients with OC, 28 (65.1%) had hematological AEs of ≥ grade 1, including thrombocytopenia (39.5%), leukopenia (37.2%), and anemia (34.9%). Ten (23.3%) patients developed grade 3/4 hematological AEs, including thrombocytopenia (11.6%), leukopenia (9.3%), and anemia (7.0%). Among the individuals who developed AEs during treatment, 9 (32.1%) patients had their treatment interrupted, with treatment being restarted in 8 (28.6%) cases, and 4 (14.3%) patients had the drug dose decreased. No deaths were reported. The median times to the occurrence of any-grade leukopenia, anemia, and thrombocytopenia were 30 (range, 7 to 162), 34 (range, 7 to 108), and 20 (range, 13 to 180) days, respectively. Most AEs occurred within the first 3 months of treatment (93.8% leukopenia, 80.0% anemia, and 76.5% thrombocytopenia). Treatments for AEs included supplementation of recombinant human granulocyte colony-stimulating factor (n=5, 17.9%), erythrocytes (n=2, 7.1%), and recombinant human thrombopoietin (n=5, 17.9%).ConclusionsThe incidence of adverse hematological reactions to an ISD of niraparib in Chinese patients with advanced OC is relatively lower in the real world than in the phase III clinical trials PRIMA (also an ISD) and NOVA. These hematological AEs can be managed through dose adjustment and symptomatic therapy.
| S-EPMC8184470 | biostudies-literature
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.
| S-EPMC6912318 | biostudies-literature
Project description:BackgroundAlthough olaparib, the first poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor approved, has been used in routine clinical practice for over three years, little has been published on its uptake, utilization patterns, and clinical outcomes.ObjectiveTo examine real-world use and outcomes of olaparib treatment in Swedish patients during the first three years following regulatory approval.Patients and methodsThis is a population-based cohort study using data from the Swedish national registers. All individuals initiating olaparib treatment from regulatory approval to 31 December 2017 were included. The extent of off-label use was assessed based on recorded diagnoses. Ovarian cancer patients were followed until death or the end of the study period. Starting dose and dose adjustments were assessed. Time to olaparib discontinuation and overall survival were plotted using Kaplan-Meier survival curves.ResultsWe identified 109 patients to whom olaparib was dispensed in Sweden during the study period. Nine of these were prescribed olaparib off-label for either breast or prostate cancer and were excluded from further analyses. Median age among the remaining 100 patients with ovarian cancer was 59 years (range: 42-83). Almost all patients (96%) started on the recommended dose (400 mg [eight capsules] taken twice daily). Dose reductions were explicitly recorded for 14% of patients. Median time to discontinuation was 289 days (95% confidence interval [CI]: 226; 338). Median overall survival from olaparib initiation was 1002 days (95% CI: 676; not calculable).ConclusionsTo our knowledge, this is the first population-based study of olaparib real-world use and outcomes. During the first three years following regulatory approval, olaparib was mainly prescribed to ovarian cancer patients. Ovarian cancer patients stayed on olaparib for a median of 9.5 months and the treatment appeared to be well tolerated.
| S-EPMC6297279 | biostudies-literature
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: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:Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.
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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.
| S-EPMC6092048 | biostudies-literature
Project description:BackgroundFor patients with advanced non-small cell lung carcinoma (NSCLC), immune checkpoint inhibitor (ICPI) and chemotherapy (chemo) ICPI represent two distinct first-line standard-of-care regimens without clear and established biomarkers to inform the optimal choice for individual patients. Here, we examined the complementary roles of tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) immunohistochemistry (IHC) to inform first-line therapy using a large real-world (rw) data set.Materials and methodsThe study included patients with NSCLC from an rw de-identified clinico-genomic database. All patients underwent genomic testing using Foundation Medicine's tissue comprehensive genomic profiling assay and PD-L1 IHC assay scored for tumor cell staining (TS).ResultsOf 2165 patients included in the analysis, 150 exhibited durable benefit from first-line ICPI regimens (these patients were enriched for PD-L1 TS ≥50, non-squamous histology, and TMB ≥20 mutations/megabase (muts/Mb)). Comparing low TMB (<10 muts/Mb), high TMB (10-19 muts/Mb), and very high TMB (≥20 muts/Mb) receiving ICPI alone, we observed a stepwise increase in median rwPFS (real world-progression free survival) (6.5, 7.5, 17.2 months) and rwOS (real world-overall survival) (10.1, 11.8, 26.9 months) as TMB increased. In the low PD-L1 (TS <50%) cohort, TMB <20 muts/Mb showed a more favorable rwPFS (HR: 0.56 (95% CI: 0.40 to 0.79)) and rwOS (HR 0.74 (95% CI: 0.58 to 0.96)) on chemoICPI when compared with ICPI alone while the point estimate in rwPFS favored monoICPI in the TMB ≥20 muts/Mb cohort, the CI is wide and does not reach statistical significance (HR: 1.68 (95% CI: 0.52 to 5.48)).ConclusionThis study provides evidence that higher TMB cut-offs, such as 20 muts/Mb, can identify patients with prolonged benefit from ICPI. TMB ≥20 muts/Mb is a potential biomarker that may identify patients in whom an ICPI without chemo could be considered, even in the setting of lower PD-L1 levels. Prospective validation of these findings could increase access to chemo-sparing regimens for the first-line treatment of advanced NSCLC.
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