Prognostic, predictive and potential surrogate markers in castration-resistant prostate cancer

Aziz, Atiqullah; Kempkensteffen, Carsten; May, Matthias; Lebentrau, Steffen; Burger, Maximilian; Chun, Felix K.‐H.; Brookman‐May, Sabine

doi:10.1586/14737140.2015.1038247

Cited by 6 publications

(5 citation statements)

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“…GS may have reduced prognostic significance in mCRPC compared with earlier disease, although a higher GS, which might increase during the natural history of the disease, has been associated with shorter OS [1,23]. There are, however, several considerations when analyzing the predictive or prognostic value of GS in clinical trials and routine clinical practice in mCRPC patients.…”

Section: Discussionmentioning

confidence: 99%

“…The therapeutic landscape in metastatic castration-resistant prostate cancer (mCRPC) has expanded in recent years with the introduction of several novel anticancer drugs prolonging overall survival (OS), including the CYP17 inhibitor abiraterone acetate (AA), the androgen-receptor antagonist enzalutamide, the radioisotope alpharadin (radium-223), the taxane cabazitaxel, and the vaccine sipuleucel-T (marketing authorization withdrawn in the European Union) [1][2][3]. These treatment options exploit different mechanisms of action; therefore, different biomarkers and prognostic variables are most relevant to measuring and predicting treatment response for different agents.…”

Section: Introductionmentioning

confidence: 99%

“…Independent predictors of OS previously identified include, but are not limited to, tumor-associated markers such as prostate-specific antigen (PSA) and Gleason score (GS), bone turnover markers such as alkaline phosphatase (ALP), patient-related factors such as cancer-related pain and performance status, metastatic distribution (eg, presence or absence of visceral metastases), and laboratory parameters, including hemoglobin, lactate dehydrogenase (LDH), albumin, and neutrophil-to-lymphocyte ratio [1,4]. Further research into predictors of patient response to different treatments would benefit physicians, supporting evidence-based clinical decision making on initial treatment selection and optimal sequential treatments [1].…”

Section: Introductionmentioning

confidence: 99%

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The Phase 3 COU-AA-302 Study of Abiraterone Acetate Plus Prednisone in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Stratified Analysis Based on Pain, Prostate-specific Antigen, and Gleason Score

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Phase 3 COU-AA-302 Study of Abiraterone Acetate Plus Prednisone in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Stratified Analysis Based on Pain, Prostate-specific Antigen, and Gleason Score

et al. 2018

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“…Furthermore, OS as a measure of therapeutic success becomes less useful as the course and duration of diseases such as cancer move from being acute to more chronic; longitudinal effects of chronic disease such as comorbidities and additional ongoing treatments add further limitations to OS as an outcome. 90,91 As a solution, there has recently been a steady move (by regulatory bodies) away from OS as a clinical end point measure and towards more short-term surrogate measures.…”

Section: Definition and Examples Of Surrogate Outcomesmentioning

confidence: 99%

The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal

Hettle

Corbett

Hinde

et al. 2017

Health Technol Assess

106

143

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BackgroundThe National Institute for Health and Care Excellence (NICE) commissioned a ‘mock technology appraisal’ to assess whether changes to its methods and processes are needed. This report presents the findings of independent research commissioned to inform this appraisal and the deliberations of a panel convened by NICE to evaluate the mock appraisal.MethodsOur research included reviews to identify issues, analysis methods and conceptual differences and the relevance of alternative decision frameworks, alongside the development of an exemplar case study of chimeric antigen receptor (CAR) T-cell therapy for treating acute lymphoblastic leukaemia.ResultsAn assessment of previous evaluations of regenerative medicines found that, although there were a number of evidential challenges, none was unique to regenerative medicines or was beyond the scope of existing methods used to conceptualise decision uncertainty. Regarding the clinical evidence for regenerative medicines, the issues were those associated with a limited evidence base but were not unique to regenerative medicines: small non-randomised studies, high variation in response and the intervention subject to continuing development. The relative treatment effects generated from single-arm trials are likely to be optimistic unless it is certain that the historical data have accurately estimated the efficacy of the control agent. Pivotal trials may use surrogate end points, which, on average, overestimate treatment effects. To reduce overall uncertainty, multivariate meta-analysis of all available data should be considered. Incorporating indirectly relevant but more reliable (more mature) data into the analysis can also be considered; such data may become available as a result of the evolving regulatory pathways being developed by the European Medicines Agency. For the exemplar case of CAR T-cell therapy, target product profiles (TPPs) were developed, which considered the ‘curative’ and ‘bridging to stem-cell transplantation’ treatment approaches separately. Within each TPP, three ‘hypothetical’ evidence sets (minimum, intermediate and mature) were generated to simulate the impact of alternative levels of precision and maturity in the clinical evidence. Subsequent assessments of cost-effectiveness were undertaken, employing the existing NICE reference case alongside additional analyses suggested within alternative frameworks. The additional exploratory analyses were undertaken to demonstrate how assessments of cost-effectiveness and uncertainty could be impacted by alternative managed entry agreements (MEAs), including price discounts, performance-related schemes and technology leasing. The panel deliberated on the range of TPPs, evidence sets and MEAs, commenting on the likely recommendations for each scenario. The panel discussed the challenges associated with the exemplar and regenerative medicines more broadly, focusing on the need for a robust quantification of the level of uncertainty in the cost-effective estimates and the potential value of MEAs in limiting the exposure of the NHS to high upfront costs and loss associated with a wrong decision.ConclusionsIt is to be expected that there will be a significant level of uncertainty in determining the clinical effectiveness of regenerative medicines and their long-term costs and benefits, but the existing methods available to estimate the implications of this uncertainty are sufficient. The use of risk sharing and MEAs between the NHS and manufacturers of regenerative medicines should be investigated further.FundingThe National Institute for Health Research Health Technology Assessment programme.

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“…In our cohort of patients, the Gleason score did not correlate significantly with OS. Previous findings are contradictory in this regard; some found that a higher Gleason score is associated with shorter OS,22 23 while others found that a value <8 did not predict a greater benefit 24. The value of the Gleason score is well established in earlier stages of the disease, but its usefulness in mCPRC remains unclear.…”

Section: Discussionmentioning

confidence: 96%

Real-world outcomes of abiraterone and enzalutamide in first-line treatment of metastatic castration-resistant prostate cancer: which patients benefit most?

et al. 2021

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ObjectivesAbiraterone and enzalutamide are two oral novel androgen receptor axis-targeted agents approved for the treatment of castration-resistant prostate cancer (mCRPC). Despite the availability of multiple treatments, there is a need to improve the knowledge and management of these drugs in the real-world setting, especially in patient groups under-represented in clinical trials. Our aim was to review the outcome of patients with chemotherapy-naïve mCRPC treated with abiraterone or enzalutamide in routine clinical practice in order to identify factors that are predictive for response.MethodsThis observational retrospective study was performed in a Spanish tertiary hospital and included men with chemotherapy-naïve mCPRC who started treatment with abiraterone or enzalutamide between September 2012 and November 2018. The study end date was 30 October 2020.ResultsNinety patients with mCRPC were included, 57 with abiraterone and 33 with enzalutamide. Median overall survival (OS) was 26.87 months (95% CI 19.68 to 34.05), with no difference found between the two treatment groups. Nine variables were related to increased OS in the univariate analysis: Eastern Cooperative Oncology Group (ECOG) performance status (0–1 vs 2), pain (need of opioids for cancer pain), visceral disease, ≥3 bone lesions, exclusively lymph node metastases, baseline prostate specific antigen (PSA) (<50 vs ≥50 ng/dL and <20 vs ≥20 ng/dL), haemoglobin (<12 vs ≥12 g/dL) and alkaline phosphatase (≤116 vs >116 IU/L). A PSA response >50% was observed in 65 patients (76.5%). In the multivariate analysis, ECOG performance status, pain, visceral disease and alkaline phosphatase provided independent prognostic information. Median OS by Kaplan–Meier analysis was significantly longer for patients with a PSA response (32.1 vs 17.9 months; HR 0.46, 95% CI 0.27 to 0.78; p=0.003).ConclusionsThis study assessed the efficacy of abiraterone and enzalutamide in a real-world setting, including patients under-represented in pivotal studies. Some clinical factors were correlated with improved OS in chemotherapy-naïve men with mCPRC treated with these drugs.

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Prognostic, predictive and potential surrogate markers in castration-resistant prostate cancer

Cited by 6 publications

References 109 publications

The Phase 3 COU-AA-302 Study of Abiraterone Acetate Plus Prednisone in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Stratified Analysis Based on Pain, Prostate-specific Antigen, and Gleason Score

The Phase 3 COU-AA-302 Study of Abiraterone Acetate Plus Prednisone in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Stratified Analysis Based on Pain, Prostate-specific Antigen, and Gleason Score

The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal

Real-world outcomes of abiraterone and enzalutamide in first-line treatment of metastatic castration-resistant prostate cancer: which patients benefit most?

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