Only One-Third of Trials Supporting FDA Approval of Cancer Drugs Met the ESMO-MCBS Criteria for Substantial Clinical Benefit
The only single-arm cancer trials to show a substantial benefit were those for osimertinib for T790-mutated NSCLC and crizotinib for ALK-rearranged NSCLC.
When the European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) was used to evaluate trials in cancer that were the basis of US Food and Drug Administration (FDA) approvals, researchers found that only one-third of the studies demonstrated a substantial clinical benefit, which was defined as grade A or grade B for trials meant to eliminate disease and grade 4 or grade 5 for trials of noncurative intent.1
The research, published in JAMA Oncology, included 133 studies that supported the approval of anticancer medications from January 1, 2006, to December 31, 2016.
Of these trials, 45 (33.8%) met the criteria for substantial clinical benefit as judged by ESMO-MCBS. There was a total of 27 single-arm trials included in the analysis, and only 2 single-arm trials (7.4%) met this threshold of benefit. The trials that got the greenlight based on the ESMO framework studied osimertinib for T790-mutated non-small cell lung cancer (NSCLC) and crizotinib for ALK-rearranged NSCLC. Both of these trials were scored as grade 4.
Of the remaining single-arm trials, 8 trials (29.6%) scored 3, 8 trials (29.8%) scored 2, 5 trials (18.5%) scored 1, and 4 trials (14.8%) scored 0.
Despite the small number of single-arm trials that met ESMO-MCBS parameters, objective response rate is “a common end point in single-arm studies supporting accelerated approval of anticancer therapies,” the researchers wrote.
For a drug to be considered to have a substantial benefit under the terms of the ESMO-MCBS scale, the authors noted, a single-arm trial not only has to be efficacious, it also has to include information on patient quality of life and postmarketing data. The low number of single-arm trials that were found to show a substantial benefit compared with randomized controlled trials “may reflect a lack of supporting data or unrealistic thresholds in the ESMO framework,” concluded the authors.
- Tibau A, Molto C, Borrell M, et al. Magnitude of clinical benefit of cancer drugs approved by the US Food and Drug Administration based on single-arm trials [published online September 27, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.4300