What is the survival benefit of receiving unapproved cancer drugs being tested in randomized clinical trials?
Saturday, October 14, 2023
9:00 AM – 10:15 AM ET
Location: Galena (Fourth Floor)
Many advanced disease patients participate in clinical trials to access new drugs that are otherwise unavailable. To what extent does trial participation lead to meaningful gains in survival? All prior attempts to answer this question have focused on relative gains in survival, rather than absolute gains. We performed a meta-analysis to estimate the absolute progression-free and overall survival advantage of being assigned to experimental arms in randomized clinical trials of new cancer drugs. We sampled 128 pre-license randomized clinical trials (involving 141 comparisons) from ClinicalTrials.gov (2017-2021). Using a random effects model for progression-free survival, the meta-analysis showed a hazard ratio of 0.80 (95% CI, 0.75-0.85), indicating benefit for patients assigned to experimental arms. This corresponded to a median progression-free survival gain of 1.26 months. For overall survival, the hazard ratio was 0.91 (95% CI, 0.88-0.95), and there was a 1.18-month gain favouring experimental arm patients. Phase 3 trials (1.74 months) and trials sponsored by large pharmaceutical companies (2.06 months) were associated with greater median progression-free survival gains for experimental arm patients than phase 2 trials (0.35 months) and trials not sponsored by large pharmaceutical companies (0.50 months). In conclusion, assignment to experimental arms produces survival gains that are statistically significantly greater than assignment to comparators. However, the absolute gain in survival is limited: slightly over one month. This result has ethical implications on access to experimental treatments, perceptions towards randomization, and selection of inferior comparators, which are all relevant to patients making decisions on clinical trial enrollment.
Hannah Moyer, BSc – Department of Equity, Ethics, and Policy – McGill University; Dean Fergusson, PhD, MHA – Medicine, Surgery, and the School of Epidemiology and Public Health – University of Ottawa; Sean McGrath, AM, BSc – Biostatistics – Harvard University; Andrea Benedetti, PhD – Epidemiology, Biostatistics & Occupational Health – McGill University; Jonathan Kimmelman, PhD – Equity, Ethics, and Policy – McGill University