scholarly journals Acute Myeloid Leukemia/Myelodysplastic Syndrome (AML/MDS) Associated with PARP Inhibitors: A Real-World Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-19
Author(s):  
Ajeet Gajra ◽  
Marjorie E Zettler ◽  
Andrew J Klink ◽  
Bruce Feinberg
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Real World ◽  
Case Reports ◽  
Statistical Significance ◽  
Clinical Trial Data ◽  
The United States ◽  
Real World Data ◽  
Peritoneal Cancer ◽  
Post Marketing

Introduction: Poly (ADP-ribose) polymerase inhibitors (PARPi's) represent a newer class of antineoplastic agents targeting cancers with defective DNA-damage repair. PARPi's indications include subtypes of ovarian, fallopian tube and primary peritoneal cancer as well as subsets of patients with breast pancreatic and prostate cancers. There are currently 4 PARPi approved by the Food and Drug Administration (FDA): olaparib (approved 12/19/2014), rucaparib (approved 12/19/2016), niraparib (approved 3/27/2017), and talazoparib (approved 10/16/2018). The incidence of AML/MDS is known to be increased following chemotherapy, with a standardized incidence ratio (observed number of cases of AML/MDS among those treated with chemotherapy/expected number of cases in the general population) of 5.8 among patients with ovarian cancer, and 3.8 among patients with breast cancer (Morton et al, JAMA Onc 2018). All 4 PARPi also carry the potential risk of AML/MDS as an adverse event (AE), but a causal relationship has not been established. Notably, almost all patients treated with a PARPi would have exposure to cytotoxic chemotherapy prior to or during PARPi therapy. For patients treated with PARPi's in clinical trials, the duration of therapy prior to cases of AML/MDS emerging ranged from <1 month to 28 months. The incidence of AML/MDS observed in clinical trials with olaparib was <1.5%, rucaparib 1.1%, niraparib 0.8%, and talazoparib 0.3%. Real-world data regarding this rare but life-threatening AE in PARPi-treated patients is needed. We evaluated reports of AML/MDS associated with PARPi's in the post-approval setting. Methods: The FDA Adverse Events Reporting System (FAERS) database was queried for AEs associated with any of the 4 approved PARPi's, from the date of the initial FDA approval for each agent (irrespective of the indication) through March 31, 2020. The FAERS database contains de-identified reports of product-related AEs, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and classified as serious or non-serious. Cases reported outside the United States were excluded. The proportion of AML/MDS reports was analyzed overall and by PARPi. To account for the variation in length of time on the market due to the different approval dates, reports of AML/MDS for each PARPi were analyzed in the first 17 months after approval (the post-marketing period for the most recently approved agent). The indication for which the PARPi was used, the sex and age of the patient experiencing the AE, and the seriousness and outcome of the AE were assessed. Comparisons of the proportion of AML/MDS cases by agent were made using the Chi-square test; statistical significance was determined at a two-sided α=0.05. Results: A total of 12823 post-marketing AE reports were associated with PARPi's, with 88 (0.7%) reporting cases of AML/MDS (Table). The largest proportion of AML/MDS cases were associated with olaparib (54 of a total of 2121 AE reports; 2.5%, p<0.00001 vs. all other PARPi), followed by niraparib (23 of a total of 5879 AE reports; 0.4%) and rucaparib (11 of a total of 4707 AE reports; 0.2%). No AML/MDS cases were associated with talazoparib (0 of a total 116 AE reports). During the first 17 months following each agent's approval, 14 cases of AML/MDS were reported in association with olaparib, 10 with rucaparib, 9 with niraparib, and 0 with talazoparib. The majority of cases of AML/MDS occurred in women (73%), and the most common indication for treatment was ovarian cancer (52%). The median age of the patients in the AML/MDS reports was 66 years. Nearly all cases were classified as serious (98%), and the outcome of the AE was death for 28% of cases, hospitalization for 17% of cases. Conclusions: Our retrospective analysis found that AML/MDS associated with PARPi's was reported rarely in the post-marketing setting, and that 60% involved olaparib. This study is limited by its retrospective design, and the possibility of under-reporting of cases to the FAERS database. Additionally, the time elapsed since approval differed by agent, and lower observed incidence of AML/MDS for some agents may reflect the limited duration of surveillance. No data is available in the case reports regarding length of exposure to chemotherapy. This real-world analysis complements existing clinical trial data and provides insight into AML/MDS associated with 4 different PARPi's in clinical practice. Disclosures Gajra: Cardinal Health: Current Employment. Zettler:Cardinal Health: Current Employment. Klink:Cardinal Health: Current Employment. Feinberg:Cardinal Health: Current Employment.

The rate of tumor growth, g, as a biomarker for overall survival (OS) in prostate cancer (PC) in clinical trials as well as in real-world data from the Veterans Administration Medical Centers (VAMCs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5074-5074
Author(s):  
Harshraj Leuva ◽  
Mengxi Zhou ◽  
Julia Wilkerson ◽  
Keith Sigel ◽  
Ta-Chueh Hsu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Tumor Growth ◽  
Real World ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Real World Data ◽  
World Data

5074 Background: Novel assessments of efficacy are needed to improve determination of treatment outcomes in clinical trials and in real-world settings. Methods: Cancer treatments usually lead to concurrent regression and growth of the drug-sensitive and drug-resistant fractions of a tumor, respectively. We have exploited novel methods of analysis that assess these two simultaneous processes and have estimated rates of tumor growth ( g) and regression ( d) in over 30,000 patients (pts) with diverse tumors. Results: In prostate cancer (PC) we have analyzed both clinical trial and real-world data from Veterans. Using clinical trial data from 6819 pts enrolled in 15 treatment arms we have established separately and by combining all the data that g correlates highly (p<0.0001) with overall survival (OS) – slower g associated with better OS. In PC, abiraterone (ABI) and docetaxel (DOC) are superior to placebo, prednisone and mitoxantrone. ABI (median g =0.0017) is superior to DOC ( g=0.0021) in first line (p=0.0013); and ABI in 2nd line ( g=0.0034) is inferior to ABI in 1st line ( g=0.0017; p<0.0001). Finally, using combined clinical trial data as a benchmark we could assess the efficacy of novel therapies in as few as 30-40 patients. Amongst 7457 Veterans, the median g on a taxane ( g=0.0022) was similar to that from clinical trials ( g=0.0012). Although only 258 Veterans received cabazitaxel (CAB), g values for CAB ( g=0.0018) and DOC ( g=0.0023) were indistinguishable (p=0.3) consistent with their identical mechanism of action. Finally, outcomes with DOC in African American (AA) ( g=0.00212) and Caucasian ( g=0.00205) Veterans were indistinguishable (p=0.9) and comparable across all VAMCs. Conclusions: The rate of tumor growth, g, is an excellent biomarker for OS both in clinical trials and in real-world settings. g allows comparisons between trials and for large trial data sets to be used as benchmarks of efficacy. Real-world outcomes in the VAMCs are similar to those in clinical trials. In the egalitarian VAMCs DOC efficacy in PC is comparable in AA and Caucasian Veterans -- indicating inferior outcomes reported in AAs are likely due to differential health care access, not differences in biology.

scholarly journals Comparing SDTM and FHIR® for Real World Data from Electronic Health Records for Clinical Trial Submissions

2021 ◽  
Author(s):  
Sarah Riepenhausen ◽  
Cornelia Mertens ◽  
Martin Dugas
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Electronic Health Records ◽  
Real World ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Real World Data ◽  
Health Records ◽  
World Data ◽  
Data Submission

Real world data for use in clinical trials is promising. We compared the SDTM for clinical trial data submission with FHIR® for routine documentation. After categorization of variables by relevance, clinically relevant SDTM items were mapped to FHIR®. About 30% in both were seen as clinically relevant. The majority of these SDTM items were mappable to FHIR® Observation resource.

scholarly journals Tuberculosis and viral hepatitis in patients treated with certolizumab pegol in Asia-Pacific countries and worldwide: real-world and clinical trial data

2020 ◽  
Author(s):  
Chak Sing Lau ◽  
Yi-Hsing Chen ◽  
Keith Lim ◽  
Marc de Longueville ◽  
Catherine Arendt ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Viral Hepatitis ◽  
Central Europe ◽  
Real World ◽  
Certolizumab Pegol ◽  
Safety Data ◽  
Asia Pacific ◽  
Hbv Reactivation ◽  
Post Marketing

Abstract Introduction/objectives To evaluate the incidence rate (IR) of tuberculosis (TB) and viral hepatitis B and C (HBV/HCV) during certolizumab pegol (CZP) treatment, worldwide and in Asia-Pacific countries, across clinical trials and post-marketing reports (non-interventional studies and real-world practice). Method CZP safety data were pooled across 49 clinical trials from 1998 to June 2017. Post-marketing reports were from initial commercialization until March 2015 (TB)/February 2017 (HBV/HCV). All suspected TB and HBV/HCV cases underwent centralized retrospective review by external experts. Incidence rates (IRs) were calculated per 100 patient-years (PY) of CZP exposure. Results Among 11,317 clinical trial patients (21,695 PY), 62 TB cases were confirmed (IR 0.29/100 PY) including 2 in Japan (0.10/100 PY) and 3 in other Asia-Pacific countries (0.58/100 PY). From > 238,000 PY estimated post-marketing CZP exposure, there were 31 confirmed TB cases (0.01/100 PY): 5 in Japan (0.05/100 PY), 1 in other Asia-Pacific countries (0.03/100 PY). Reported regional TB IRs were highest in eastern Europe (0.17/100 PY), central Europe (0.09/100 PY), and Mexico (0.16/100 PY). Across clinical trials, there was 1 confirmed HBV reactivation and no HCV cases. From > 420,000 PY estimated post-marketing CZP exposure, 5 HBV/HCV cases were confirmed (0.001/100 PY): 2 HCV reactivations; 1 new HCV; plus 2 HBV reactivations in Japan (0.008/100 PY). Conclusions CZP TB risk is aligned with nationwide TB rates, being slightly higher in Asia-Pacific countries excluding Japan. Overall, TB and HBV/HCV risk with CZP treatment is currently relatively low, as risk can be minimized with patient/physician education, screening, and vigilant treatment, according to international guidelines. Key Points:• TB rates were highest in eastern/central Europe, Mexico, and Asia-Pacific regions.• With the implementation of stricter TB screening and risk evaluations in 2007, especially in high TB incidence countries, there was a notable reduction TB occurrence.• Safety profile of biologics in real-world settings complements controlled studies.• TB and hepatitis (HBV/HCV) risk with certolizumab pegol (CZP) treatment is low.

scholarly journals Real-World Data for Planning Eligibility Criteria and Enhancing Recruitment: Recommendations from the Clinical Trials Transformation Initiative

2021 ◽  
Author(s):  
Scott R. Evans ◽  
Dianne Paraoan ◽  
Jane Perlmutter ◽  
Sudha R. Raman ◽  
John J. Sheehan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Real World Data ◽  
Eligibility Criteria ◽  
World Data ◽  
Study Planning ◽  
Efficiency And Effectiveness ◽  
Multi Stakeholder ◽  
Functional Teams ◽  
Data Driven Decisions

AbstractThe growing availability of real-world data (RWD) creates opportunities for new evidence generation and improved efficiency across the research enterprise. To varying degrees, sponsors now regularly use RWD to make data-driven decisions about trial feasibility, based on assessment of eligibility criteria for planned clinical trials. Increasingly, RWD are being used to support targeted, timely, and personalized outreach to potential trial participants that may improve the efficiency and effectiveness of the recruitment process. This paper highlights recommendations and resources, including specific case studies, developed by the Clinical Trials Transformation Initiative (CTTI) for applying RWD to planning eligibility criteria and recruiting for clinical trials. Developed through a multi-stakeholder, consensus- and evidence-driven process, these actionable tools support researchers in (1) determining whether RWD are fit for purpose with respect to study planning and recruitment, (2) engaging cross-functional teams in the use of RWD for study planning and recruitment, and (3) understanding patient and site needs to develop successful and patient-centric approaches to RWD-supported recruitment. Future considerations for the use of RWD are explored, including ensuring full patient understanding of data use and developing global datasets.

scholarly journals 510 Niraparib outcomes in brca wild-type platinum sensitive recurrent ovarian cancer: a comparison of real-world data to the nova trial

2020 ◽  
Author(s):  
Douglas Cartwright ◽  
Patricia Roxburgh ◽  
Barbara Stanley ◽  
Jennifer Brown ◽  
Alistair Mclaren ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real World ◽  
Recurrent Ovarian Cancer ◽  
Wild Type ◽  
Real World Data ◽  
World Data ◽  
Platinum Sensitive

scholarly journals LDL-cholesterol change and goal attainment following statin intensity titration among Asians in primary care: a retrospective cohort study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Hao Sen Andrew Fang ◽  
Qiao Gao ◽  
Mong Li Lee ◽  
Wynne Hsu ◽  
Ngiap Chuan Tan
Keyword(s):  
Primary Care ◽  
Clinical Trials ◽  
Cohort Study ◽  
Real World ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Goal Attainment ◽  
Real World Data ◽  
World Data ◽  
Asian Patients

Abstract Background Clinical trials have demonstrated that either initiating or up-titrating a statin dose substantially reduce Low-Density Lipoprotein-Cholesterol (LDL-C) levels. However, statin adherence in actual practice tends to be suboptimal, leading to diminished effectiveness. This study aims to use real-world data to determine the effect on LDL-C levels and LDL-C goal attainment rates, when selected statins are titrated in Asian patients. Methods A retrospective cohort study over a 5-year period, from April 2014 to March 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of Dyslipidaemia in a primary care clinic in Singapore. The statins were classified into low-intensity (LI), moderate-intensity (MI) and high-intensity (HI) groups according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Patients were grouped into “No statin”, “Non-titrators” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the mean percentage change in LDL-C and absolute change in LDL-C goal attainment rates were computed for each permutation of statin intensity titration. Results Among the cohort of 11,499 patients, with a total of 266,762 visits, there were 1962 pairs of LDL-C values associated with a statin titration. Initiation of LI, MI and HI statin resulted in a lowering of LDL-C by 21.6% (95%CI = 18.9–24.3%), 28.9% (95%CI = 25.0–32.7%) and 25.2% (95%CI = 12.8–37.7%) respectively. These were comparatively lower than results from clinical trials (30 to 63%). The change of LDL-C levels due to up-titration, down-titration, and discontinuation were − 12.4% to − 28.9%, + 13.2% to + 24.6%, and + 18.1% to + 32.1% respectively. The improvement in LDL-C goal attainment ranged from 26.5% to 47.1% when statin intensity was up-titrated. Conclusion In this study based on real-world data of Asian patients in primary care, it was shown that although statin titration substantially affected LDL-C levels and LDL-C goal attainment rates, the magnitude was lower than results reported from clinical trials. These results should be taken into consideration and provide further insight to clinicians when making statin adjustment recommendations in order to achieve LDL-C targets in clinical practice, particularly for Asian populations.

Abstract 1122‐000142: Safety and Efficacy of Surpass Streamline for Intracranial Aneurysms: A Multicenter US Real‐World Experience (SESSIA)

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Juan Vivanco‐Suarez ◽  
Alan Mendez‐Ruiz ◽  
Farooqui Mudassir ◽  
Cynthia B Zevallos ◽  
Milagros Galecio‐Castillo ◽  
...  
Keyword(s):  
Real World ◽  
Intracranial Aneurysms ◽  
The United States ◽  
Chromium Alloy ◽  
Cobalt Chromium ◽  
Anterior Circulation ◽  
Safety And Efficacy ◽  
Post Marketing ◽  
The Mean

Introduction : Flow diversion has established itself as standard treatment of wide complex intracranial aneurysms (IA). Its recognition has been validated with positive occlusion rates and favorable clinical outcomes. The Surpass Streamline (SS) flow diverter (FD) is a braided cobalt/chromium alloy implant with 72 or 96 wires approved by the FDA in 2018. The aim of this study is to determine the safety and efficacy of the SS in a post‐marketing large US cohort. Methods : We performed a multicenter, retrospective study for consecutive patients treated with the SS FD for IA between January 2018 and June 2021 in the United States. Inclusion criteria for participants were: 1. Adults (≥ 18 years) and 2. Treatment with SS FD for IA. Primary safety end point was a major ipsilateral stroke (increase in National Institutes of Health Stroke Scale Score of ≥ 4) or neurological death within 12 months. Primary efficacy was assessed using the 3‐point Raymond‐Roy (RR) occlusion scale on digital subtraction angiography (DSA) at 6‐12‐month follow‐up. Results : A total of 276 patients with 313 aneurysms were enrolled. The median age was 59 years and 199 (72%) were females. The most common comorbidities included hypertension in 156 (57%) subjects followed by hyperlipidemia in 76 (28%) patients. One hundred and twenty‐two (44%) patients were asymptomatic while subarachnoid hemorrhage was present in only 10 (4%) patients. A total of 143 (46%) aneurysms were left‐sided. Aneurysms were located as follows: 274 (88%) were in the anterior circulation with paraophthalmic being the most common in 120 (38%) followed by petrocavernous ICA in 81 (26%); 33 (11%) aneurysms were located in the posterior circulation with basilar trunk being the most common in 14 (5%). The mean maximum aneurysm dome width was 5.77 ± 4.7 mm, neck width 4.22 ± 3.8 mm and dome to neck ratio was 1.63 ± 1.3 mm. The mean number of SS FD implanted per aneurysm was 1.06 (range 1–3) with more than one SS FD implanted in 21 (7%) aneurysms. Modified Rankin Scale (mRS) of 0–2 was present in 206/213 (97%) patients at 6–12 month follow‐up. The complete aneurysm occlusion (RR 1) rate was 145/175 (83%) among subjects who had angiographic follow‐up at 6–12 months. Major stroke and death was encountered in 7 (2%) and 5 (1.8%) of the patients respectively. Conclusions : Our data represent the largest real‐world study using SS FD. These results corroborate its post‐marketing safety and efficacy for the treatment of intracranial aneurysms showing more favorable rates to the initial experience during SCENT trial.

Real-world utilization and costs with biosimilar and reference filgrastim in patients with breast cancer receiving myelosuppressive chemotherapy in a community oncology setting from 2015 to 2017.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 57-57
Author(s):  
Robert M. Rifkin ◽  
Lisa Herms ◽  
Chuck Wentworth ◽  
Anupama Vasudevan ◽  
Kimberley Campbell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real World ◽  
Initial Period ◽  
The United States ◽  
Time Frame ◽  
Real World Data ◽  
Electronic Health Record Data ◽  
Myelosuppressive Chemotherapy ◽  
Community Oncology ◽  
The Us

57 Background: Biosimilars have potential to reduce healthcare costs and increase access in the United States, but lack of uptake has contributed to lost savings. Filgrastim-sndz was the first FDA-approved biosimilar, and much can be learned by evaluating its uptake. In February 2016, the US Oncology Network converted to filgrastim-sndz as its short-acting granulocyte colony-stimulating factor (GCSF) of choice for prevention of febrile neutropenia (FN) following myelosuppressive chemotherapy (MCT). To understand utilization and cost patterns, this study analyzes real-world data of GCSFs within a community oncology network during the initial period of conversion to the first biosimilar available in the US. Methods: This descriptive retrospective observational study used electronic health record data for female breast cancer (BC) patients receiving GCSF and MCT at high risk of FN. Patient cohorts were defined by first receipt of either filgrastim or filgrastim-sndz during the 410 days before and after biosimilar conversion. Healthcare resource utilization (HCRU) and costs for GCSF and complete blood counts (CBC) were collected at GCSF initiation through the earliest of 30 days following end of MCT, loss to follow up, death, or data cutoff. Results: 146 patients were identified: 81 (55.5%) filgrastim and 65 (44.5%) filgrastim-sndz. No directional differences existed in baseline characteristics between the cohorts. Higher proportions of filgrastim-sndz patients received dose-dense MCT (33.8% vs 22.2%). Time trends show an initial spike in HCRU and cost for filgrastim-sndz patients after formulary conversion, which subsequently decreased and converged to that of the filgrastim cohort after 12 months. When aggregated, the overall median total administration counts, per patient per month (PPPM) and dosage, were marginally higher for filgrastim-sndz (5 vs 3; 2.9 vs 1.4; 1920 vs 1440 mcg, respectively). Median PPPM costs were higher for filgrastim-sndz ($803 vs $545). Median CBC utilization and costs were higher for filgrastim-sndz (2.8 vs 2.5; $28 vs $23, respectively). Conclusions: This study provides insight into real-world HCRU and cost patterns after formulary conversion to a biosimilar for BC patients receiving MCT and GCSF. As a descriptive study, causal inferences cannot be made and an underlying effect from index chemotherapy cannot be excluded. Convergence of HCRU and costs after 12 months suggests that overall results may be driven by behavior at initial formulary switch. Since filgrastim-sndz was the first US biosimilar approved, the uptake may be indicative of an experience with biosimilar acceptance in general. Future real-world studies of biosimilars must consider inconsistent utilization and practice trends during the time frame directly following formulary conversion.

Sign in / Sign up

Export Citation Format

Share Document