Quantifying the Survival Benefits of Oncology Drugs With a Focus on Immunotherapy Using Restricted Mean Survival Time

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  • a Sunnybrook Research Institute;
  • b Odette Cancer Centre, Sunnybrook Health Sciences Centre;
  • c Department of Medicine, University of Toronto; and
  • d Canadian Centre for Applied Research in Cancer Control, Toronto, Ontario, Canada.
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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.

Submitted May 1, 2019; accepted for publication September 18, 2019.

Previous presentation: An abstract of this study was presented at the 2018 ASCO Annual Meeting, June 1–8, 2018, in Chicago, Illinois (Abstract 6617), and the Canadian Centre for Applied Research in Cancer Control 7th Annual Conference, May 27–28, 2018, in Montreal, Quebec (Abstract 131).

Author contributions: Study design: Everest, Chan. Literature search and data extraction: Parshad, Everest. Data review and statistical analyses: Rahmadian, Delos Santos. Data interpretation: Chan. Manuscript writing: Rahmadian, Delos Santos, Cheung, Chan.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: The Canadian Centre for Applied Research in Cancer Control (ARCC) received core funding from the Canadian Cancer Society Research Institute through grant 2105-703549.

Correspondence: Kelvin K. Chan, MD, MSc, PhD, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5 Canada. Email: kelvin.chan@sunnybrook.ca
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