Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Feb;14(1):31-38.
doi: 10.1007/s11899-019-0495-9.

Should Overall Survival Remain an Endpoint for Multiple Myeloma Trials?

Sarah A Holstein  1 , Vera J Suman  2 , Philip L McCarthy  3
Affiliations
Review

Should Overall Survival Remain an Endpoint for Multiple Myeloma Trials?

Sarah A Holstein et al. Curr Hematol Malig Rep. 2019 Feb.

Abstract

Purpose of review: While the traditional gold standard for demonstrating clinical benefit of a therapy has been to show prolongation of overall survival (OS), there are multiple factors which can hinder the use of OS as a primary endpoint in randomized clinical trials (RCTs). Here, we analyze recent myeloma RCTs and evaluate the issues relevant to current and future myeloma RCT design.

Recent findings: A review of recent phase III RCTs that led to approval of new agents/combinations reveals that none were designed with OS as the primary endpoint, but instead utilized time to progression (TTP) or progression-free survival (PFS). These studies illuminate the inherent difficulties of designing trials with the primary endpoint of OS/PFS in a disease characterized by increasingly prolonged survival times, availability of effective salvage therapies, and competing events such as co-morbid conditions. Alternative primary endpoints other than OS or PFS need to be developed for future myeloma RCTs. Validated surrogate endpoints with novel clinical trial designs will help improve the feasibility of conducting comparative clinical trials in a timely manner.

Keywords: Clinical trial; Multiple myeloma; Overall survival; Primary endpoint.

PubMed Disclaimer

References

    1. Costa LJ, Brill IK, Omel J, Godby K, Kumar SK, Brown EE. Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States. Blood Adv 2017; 1: 282–7. - PMC - PubMed
    1. Johnson JR, Temple R. Food and Drug Administration requirements for approval of new anticancer drugs. Cancer Treat Rep 1985; 69: 1155–9. - PubMed
    1. Johnson JR, Williams G, Pazdur R. End points and United States Food and Drug Administration approval of oncology drugs. J Clin Oncol 2003; 21: 1404–11. - PubMed
    1. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016; 17: e328–46. - PubMed
    1. Fleming TR, Powers JH. Biomarkers and surrogate endpoints in clinical trials. Stat Med 2012; 31: 2973–84. - PMC - PubMed