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A Systematic Analysis of Post-Protocol Therapy in First Line Checkpoint Inhibitor Trials
25 Pages Posted: 1 Nov 2021More...
Although first-line approvals of checkpoint inhibitors (CPI) are often preceded by approval in the relapsed setting, many control patients in trials evaluating upfront CPI, do not receive a CPI upon disease progression. In this systematic analysis, we reviewed trials evaluating upfront use of CPI in metastatic tumors to evaluate the amount of control arm patients that receive CPI upon disease progression and the timing difference between FDA approval for a CPI in the relapsed setting and enrollment periods for first-line trials. We used the FDA website to review approvals for PD1/PD-L1 inhibitors in metastatic solid tumors through September 2021 and identified instances where a first line trial was preceded by a trial in the relapsed setting. We found 28 FDA approvals for a PD1 or PD-L1 inhibitor in the first line, with 23 instances of a first line trial preceded by a trial of the same or similar drug in the relapsed setting. We reviewed summary data from the correlating randomized trials for these approvals and found that first line trial start of accrual preceded approval of a same/similar drug by a mean of 5.4 months, median 9 months and ended accrual by a mean of 11.3, median of 14 months after approval in the relapsed setting. A mean of 53% of patients in the control arm received subsequent therapy in first-line CPI trials, with a mean of 34% of control arm patients receiving a CPI. This systematic analysis shows that many control arm patients in trials evaluating first line CPI are not exposed to CPI with known efficacy at disease progression, highlighting a need to standardize post-protocol approach to reflect evolving standards of care. This analysis is limited by a lack of individual patient level data and heterogeneity of trials.
This analysis was not registered with PROSPERO.
Funding Information: No external funding was provided for this analysis.
Declaration of Interests: The authors do not have any conflicts of interest to report.
Keywords: oncology, immunotherapy, checkpoint inhibitors, clinical trial design
Suggested Citation: Suggested Citation