2915 - Magnitude of Clinical Benefit of Cancer Drugs Approved Based on Single-Arm Trials (SAT) by the US Food and Drug Administration (FDA)

Background

The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated and reproducible tool to assess the magnitude of clinical benefit from anti-cancer drugs. In contrast to version 1.0 (v1.0) of this tool, which could be used to assess randomized controlled trials (RCT) only, the updated version 1.1 (v1.1) allows scoring of drugs approved on the basis of single-arm trials (SAT). Here, we applied the updated ESMO-MCBS v1.1 to the assessment of trials supporting FDA approval including those based on SAT.

Methods

We searched the Drugs@FDA website for anticancer drug approvals from January 2006 to December 2016. Drug labels and reports of registration trials were reviewed and study characteristics, efficacy, toxicity, and quality of life outcomes as well as regulatory pathways were collected. For RCT, ESMO-MCBS v1.0 and v1.1 grades were applied; for SAT only v1.1 was used. Substantial benefit was defined as a grade of A or B for trials of curative intent and 4 or 5 for those of palliative intent. Agreement between v1.0 and v1.1 scores was assessed using Cohen’s κ statistic.

Results

Of 134 studies supporting FDA approval, 4 reported preplanned analyses in multiple subgroups but in 5, ESMO-MCBS could not be applied. Therefore, analysis was based on 133 data points. Of these, only 45 (34%) met thresholds for substantial benefit using the ESMO-MCBS v1.1 framework. Version 1.1 of the scale facilitated grading of 27 SAT and 1 RCT which were ungradeable with v1.0. Among the 106 studies for which we could calculate scores using both v1.0 and v1.1 of the ESMO-MCBS scale, grades were identical in 96 cases (91%; κ = 0.86). In 10 trials, grades were discrepant, including 5 upgrades and 5 downgrades. We observed only one case of change in substantial benefit thresholds (1%; κ = 0.96). Only 2 SAT (7%) met the threshold for substantial clinical benefit using ESMO-MCBS v1.1.

Conclusions

In patients with advanced solid tumors, approximately one third of trials supporting FDA approval meet the threshold for substantial clinical benefit using ESMO-MCBS v1.1. Drug approvals supported by RCT were more likely to result in substantial benefit compared to approvals supported by SAT.

Clinical trial identification

Legal entity responsible for the study

Hospital de la Santa Creu i Sant Pau.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.