Patient burden and clinical advances associated with post approval monotherapy cancer drug trials: a retrospective cohort study
- Objective: The study investigates the efforts to extend the uses of new drugs by testing them for new, non-approved indications and examines the patient burden and clinical impact.
- Design and Setting: A retrospective cohort study focused on post-approval trials of anticancer drugs approved between 2005 and 2007, within 5 years after their first FDA approval. The study used data from FDA, Medline, and Embase as of February 12, 2019.
- Outcome Measures: The primary goal was to assess patient burden and clinical impact, with risks measured by severe adverse events and deaths, and clinical impact by FDA approvals, incorporation into NCCN guidelines, or progression to randomized trials.
- Results: Among 104 trials and 69 trajectories, involving 4699 patients, 19.6% experienced severe adverse events, and 2.8% experienced grade 5 events. No trajectories received FDA approval post-initial approval, 5 were recommended by NCCN, and 11 advanced to randomized testing.
- Conclusions: The study found that expanding the applications for previously approved drugs faces similar challenges as developing new drugs. These findings can guide research priorities and expectations for label-extending trials.
After new cancer drugs receive regulatory approval, researchers often pursue trials testing the drug in indications or combinations that would extend the use of the drug beyond the indication for which it was initially approved. Sometimes, such efforts are aimed at obtaining a revision to an Food and Drug Administration (FDA) label, other times they aim at discovering an off-label use that can be recommended in clinical practice guidelines. Such ‘label-extending’ trials are facilitated by the fact that newly approved cancer drugs are less likely to elicit unexpected safety issues, regulatory approval standards are weaker for post-approval trials, and the ease of testing an already approved and manufactured drug are likely to be much less as compared with a drug that has not yet received approval.
In numerous cases, label-extending trials have uncovered new uses for approved drugs—especially in the setting of rare malignancies. For example, imatinib was approved for hyper-eosinophilic syndrome, chronic eosinophilic leukemia and dermatofibrosarcoma, indications that were not launched into clinical trials until after the initial approval of imatinib in chronic myeloid leukemia. However, where much is known about the volume and clinical impact of pre-license clinical trials in cancer, there is much less systematic evidence about label-extending research activities. A previous study suggested that label-extending t