scholarly journals Cost-effective survival prediction for patients with advanced prostate cancer using clinical trial and real-world hospital registry datasets

2020 ◽  
Vol 133 ◽  
pp. 104014 ◽  
Author(s):  
Mika Murtojärvi ◽  
Anni S. Halkola ◽  
Antti Airola ◽  
Teemu D. Laajala ◽  
Tuomas Mirtti ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5074-5074
Author(s):  
Harshraj Leuva ◽  
Mengxi Zhou ◽  
Julia Wilkerson ◽  
Keith Sigel ◽  
Ta-Chueh Hsu ◽  
...  

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.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 313-313
Author(s):  
Simon Yuen Fai Fu ◽  
Paula Barlow ◽  
Carmel Maree Jacobs ◽  
Fritha J. Hanning ◽  
Peter C.C. Fong

313 Background: Docetaxel (D) chemotherapy is a standard of care in men with advanced prostate cancer (APC), both metastatic castration sensitive (CS) and castration resistant (CR) disease. The risk of significant toxicities may deter D use in elderly patients. We aim to evaluate the real world efficacy and tolerability of D in men with APC. Methods: Between 04/2014 and 05/2017, data from men aged ≥75 with APC treated at Auckland City Hospital with 3 weekly D were retrospectively collected from the genitourinary medical oncology database. Results: 33 (CS 12, CR 21) men were identified. 70% had PSA decline ≥50% (CS 92%, CR 57%). Median time to next line of therapy was 0.5 y in the CR arm. One third (n = 2/6) of CR patients on opioid had improved pain control with D. 75% had upfront dose reduction (DR). The median dose intensity was 21 mg/m2/wk (CS) and 18 mg/m2/wk (CR). 9 patients had dose escalation after upfront DR, all but 3 needed DR later, and none was escalated to 75 mg/m2. 58% (CS 75%, CR 48%) completed 6 cycles, and only 6% (n = 2) completed 6 cycles at 75 mg/m2. 24% had ≥G3 hematological toxicities. Febrile neutropenia rate was 12% (CS 8%, CR 14%). Pegfilgrastim was used in 1 CS and 1 CR men. Admission rate was 39% (CS 25%, CR 48%), 77% (CS 100%, CR 70%) was treatment related, and 23% (CR 30%) due to malignancy. 15% (CS 25%, CR 9%) required RBC transfusions. 33% CR men progressed while on treatment, and two deaths from pneumonitis and disease progression were noted. Conclusions: Docetaxel is active in elderly men with APC. Toxicities are manageable but can be life-threatening. Admission is frequent especially in CR patients. Proactive dose reduction should be considered to balance benefits vs. risks in this population. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14054-e14054
Author(s):  
Yun Mai ◽  
Kyeryoung Lee ◽  
Zongzhi Liu ◽  
Zhiqiang Li ◽  
Scott Jones ◽  
...  

e14054 Background: Matching clinical attributes (i.e. indications, lab tests, treatment regimens) of clinical trial eligibility criteria with real world patient data is extremely challenging. Attribute phenotyping is one of the key components of Trial2Patient, a customized system developed by Sema4 to find patients for clinical trials. Transforming treatment regimens to a standard ontology and encoding drugs with standard nomenclatures will facilitate the semantic retrieval of treatments mentioned in clinical trial criteria. This will also enable the interoperation between different data sources that is often required for fast-learning and scalable healthcare information system. Methods: Free text containing treatment regimen/medication terms were extracted and preprocessed from three sources: 1) clinical trials listed in a commercial database citeline.com, 2) clinical trials listed in clinicaltrials.gov, and 3) National Comprehensive Cancer Network (NCCN) Guidelines. The regimen terms such as neoadjuvant therapy for non-small cell lung cancer, checkpoint inhibitor, EGFR inhibitor, androgen deprivation therapy (ADT), among many others, were profiled by AI methods (i.e. pattern reorganization and rule-based) and knowledge engineering via Sema4’s in-house knowledge base (CAV), Pharmaprojects in citline.com and NCCN Guidelines. The drugs related to each regimen were identified and mapped to RxCUI via RxNorm ontology. Results: We identified 76 regimen terms for non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and prostate cancer (e.g. PD-L1 ≥1% nonsquamous NSCLC, bone antiresorptive therapy for M1 castration resistant prostate cancer), and 14,476 drug-category pair (e.g. pembrolizumab is a PD-1 inhibitor, pembrolizumab is used as the third line and beyond systemic therapy for M1 CRPC). All drugs identified were mapped to RxCUI for real world patient matching. Conclusions: This approach systematically extracted and normalized regimens and medications mentioned in clinical trials in NSCLC, SCLC and prostate cancer to standard codes. These standardized data can be used in mapping treatment histories of a patient to the eligibility criteria for clinical studies or for identifying studies relevant to a patient. The outcome of profiling cancer treatment regimens through standard ontology RxNorm may be particularly valuable in cancer studies based on real-world evidence.


2021 ◽  
pp. bmjspcare-2021-002994
Author(s):  
Bianca Viljoen ◽  
Michael S Hofman ◽  
Suzanne K Chambers ◽  
Jeff Dunn ◽  
Haryana Dhillon ◽  
...  

ObjectivesNested qualitative studies within clinical trials provide the opportunity to better understand participant experiences of participation and identify areas where improved support is required. The purpose of this qualitative study is to describe the lived experiences of men with advanced prostate cancer participating in the TheraP trial; a randomised trial of 177Lu-PSMA-617 compared with cabazitaxel chemotherapy.MethodsFifteen men with advanced prostate cancer were recruited from the TheraP clinical trial and interviewed at three time points during the trial. Interviews were inductively analysed using thematic analysis. This research paper reports the results from the baseline interview at commencement of the trial, focusing specifically on participants’ enrolment experiences.ResultsFour themes were identified representing the lived experiences of men with advanced prostate cancer deciding to participate in the TheraP trial: (1) hoping to survive; (2) needing to feel informed; (3) choosing to participate and (4) being randomised. The process of deciding to enrol in a clinical trial is filled with indecision, emotional difficulties and focused on a desire to live.ConclusionsFor men with advanced prostate cancer, the experience of deciding to enrol in a clinical trial is principally driven by a desire to survive but interlinked with the need to make an informed decision as participants in this study expressed a preference for allocation to the experimental arm. Men seeking to enrol in clinical trials of new prostate cancer treatments would benefit from improved informational and decision support.Trial registration numberNCT03392428, ANZUP1603.


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