RESUMO
BACKGROUND: Whether patients with excellent and reduced performance status (PS) derive different net clinical benefit from novel anticancer systemic therapies on clinical trials is unclear. MATERIALS AND METHODS: A systematic review was conducted of randomised controlled trials (RCTs) cited for drug approvals between 2006 and August 2015 by the Food and Drug Administration, the European Medicines Agency and Health Canada. Included studies had overall survival (OS) and/or progression-free survival (PFS) primary endpoints. Meta-analyses of OS/PFS based on PS dichotomised into excellent and reduced subgroups were performed using random effects. RESULTS: The systematic review identified 110 RCTs, with none reporting PS subgroup analyses for toxicity and 66 (60%) for efficacy. For these 66 RCTs involving 44 511 patients, pooled HRs for excellent and reduced groups were 0.65 (95% CI 0.61 to 0.70) and 0.67 (95% CI 0.62 to 0.72), respectively, with no difference between the two groups (p=0.68). Sensitivity analyses based on drug or cancer type and type of endpoints (OS or PFS) demonstrated similar results. CONCLUSIONS: No decrease in relative efficacy from novel systemic therapy was found for patients with reduced PS when compared with patients with excellent PS for the range which were included in modern RCTs. Reporting of PS subgroup analyses of toxicities and more inclusion of patients with borderline low PS in RCTs should be considered for a more comprehensive understanding of the net clinical benefits of contemporary systemic therapies in patients across the spectrum of different PS.
RESUMO
Purpose Whether the ASCO Value Framework and the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) measure similar constructs of clinical benefit is unclear. It is also unclear how they relate to quality-adjusted life-years (QALYs) and funding recommendations in the United Kingdom and Canada. Methods Randomized clinical trials of oncology drug approvals by the US Food and Drug Administration, European Medicines Agency, and Health Canada between 2006 and August 2015 were identified and scored using the ASCO version 1 (v1) framework, ASCO version 2 (v2) framework, and ESMO-MCBS by at least two independent reviewers. Spearman correlation coefficients were calculated to assess construct (between frameworks) and criterion validity (against QALYs from the National Institute for Health and Care Excellence [NICE] and the pan-Canadian Oncology Drug Review [pCODR]). Associations between scores and NICE/pCODR recommendations were examined. Inter-rater reliability was assessed using intraclass correlation coefficients. Results From 109 included randomized clinical trials, 108 ASCOv1, 111 ASCOv2, and 83 ESMO scores were determined. Correlation coefficients for ASCOv1 versus ESMO, ASCOv2 versus ESMO, and ASCOv1 versus ASCOv2 were 0.36 (95% CI, 0.15 to 0.54), 0.17 (95% CI, -0.06 to 0.37), and 0.50 (95% CI, 0.35 to 0.63), respectively. Compared with NICE QALYs, correlation coefficients were 0.45 (ASCOv1), 0.53 (ASCOv2), and 0.46 (ESMO); with pCODR QALYs, coefficients were 0.19 (ASCOv1), 0.20 (ASCOv2), and 0.36 (ESMO). None of the frameworks were significantly associated with NICE/pCODR recommendations. Inter-rater reliability was good for all frameworks. Conclusion The weak-to-moderate correlations of the ASCO frameworks with the ESMO-MCBS, as well as their correlations with QALYs and with NICE/pCODR funding recommendations, suggest different constructs of clinical benefit measured. Construct convergent validity with the ESMO-MCBS did not increase with the updated ASCO framework.
