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Response Rates and Durations of Response for Biomarker-Based Cancer Drugs in Nonrandomized Versus Randomized Trials

Bishal Gyawali1,2,3, Elvira D'Andrea1, Jessica M Franklin1

  • 1Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; and.

Journal of the National Comprehensive Cancer Network : JNCCN
|January 8, 2020
PubMed
Abstract

Insights

Response rates for targeted cancer drugs were similar between non-randomized controlled trials (non-RCTs) and RCTs. However, durations of response were higher in non-RCTs, suggesting potential overestimation of benefits for these cancer drugs.

Area of Science:

  • Oncology
  • Clinical Trials
  • Pharmacogenomics

Background:

  • FDA approvals for targeted cancer drugs often rely on durable responses from non-randomized controlled trials (non-RCTs).
  • The reliability of these non-RCT findings when compared to randomized controlled trials (RCTs) is a critical consideration.

Purpose of the Study:

  • To evaluate if response rates (RRs) and durations of response (DoRs) for targeted cancer drugs are consistent between non-RCTs and RCTs.
  • To assess the predictive value of non-RCT data for survival outcomes in RCTs.

Main Methods:

  • Identified cancer drugs approved based on biomarker changes using FDA data (through December 2017).
  • Extracted RRs and DoRs from available non-RCTs and RCTs for 19 drug-indication pairs.
  • Utilized random-effects meta-analysis to compare RRs and DoRs between trial types.

Main Results:

  • Response rates (RRs) were comparable between non-RCTs and RCTs (pooled ratio: 1.06).
  • Durations of response (DoRs) were significantly higher in non-RCTs compared to RCTs (pooled ratio: 1.17).
  • Data from non-RCTs were found to be poor surrogates for overall survival in RCTs.

Conclusions:

  • While response rates were similar, the significantly higher durations of response in non-RCTs suggest potential overestimation.
  • Caution is advised when using non-RCT data for durable responses in drug approval and clinical prescription.
  • Non-RCT derived response data may not accurately predict survival benefits for targeted cancer therapies.

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