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Published on: February 8, 2018
Quantifying the Survival Benefits of Oncology Drugs With a Focus on Immunotherapy Using Restricted Mean Survival Time
Amanda Putri Rahmadian1, Seanthel Delos Santos1, Shruti Parshad2
1Sunnybrook Research Institute.
Background:
Restricted mean survival time (RMST) overcomes limitations of current measures of survival benefits because it directly captures information of the entire area under Kaplan-Meier survival curves. Using RMST difference (absolute survival benefit) and RMST ratio (relative survival benefit), we quantified the magnitude of survival benefits of recent oncology drugs and compared immunotherapies with nonimmunotherapies.
Methods:
Kaplan-Meier curves were extracted from phase II/III randomized controlled trials used by the FDA for oncology drug approvals from January 2011 through November 2017 with overall survival (OS) or progression-free survival (PFS) as primary endpoints. RMST differences, ratios, and their 95% confidence intervals were meta-analyzed to estimate absolute and relative survival benefits of contemporary oncology drugs and to compare immunotherapies with nonimmunotherapies. Meta-regression was conducted to adjust for potential confounders.
Results:
Ninety-four trials with a total of 51,639 patients were included. Overall absolute survival benefits (RMST differences) were 1.55 months for OS (95% CI, 1.32-1.77) and 2.99 months for PFS (95% CI, 2.65-3.33). Overall relative survival benefits (RMST ratios) were 1.11 for OS (95% CI, 1.09-1.13) and 1.42 for PFS (95% CI, 1.36-1.48). Immunotherapy absolute PFS benefit was less than that of nonimmunotherapy (1.56 vs 3.23 months), whereas immunotherapy absolute OS benefit was larger than that of nonimmunotherapy by 0.59 months (2.02 vs 1.43 months). Adjusted OS RMST difference was 0.91 months greater for immunotherapy than for nonimmunotherapy after adjusting for confounders.
Conclusions:
Absolute survival benefits of recent oncology drugs are modest. Survival benefits of immunotherapies are not dramatically superior to those of nonimmunotherapies. Routine reporting and use of RMST may help patients, physicians, and payers make more informed and responsible decisions regarding the care of patients with cancer.
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