Assessment of Objective Response Rate by Investigator vs. Blinded Independent Central Review in Pivotal Trials of Oncology Drugs for Solid Tumor Indications.

Background/

Objective: Objective response rate (ORR) is a surrogate endpoint frequently employed in early-phase clinical trials of anticancer agents for the treatment of solid tumors. Assessments of ORR by local investigators tend to be influenced by subjective factors, and blinded independent central review (BICR) is recommended by regulatory agencies in order to detect evaluation bias. The objective of this analysis was to compare BICR-assessed vs. investigator-assessed ORRs in pivotal trials of cancer drugs recently approved by the United States Food and Drug Administration (FDA) for solid tumor indications.

Methods: The FDA's Novel Drug Approvals reports were reviewed to identify cancer therapies approved for solid tumor indications between 1 January 2020 and 30 June 2024. Among therapies with ORR as a primary endpoint in pivotal trials, and for which both BICR- and investigator-assessed ORRs were available, a pooled analysis was conducted to compare these ORRs (using the Mantel-Haenszel method). A correlation analysis was also performed to evaluate the concordance between ORR assessments.

Results: A total of 20 anticancer agents met the criteria for inclusion in this analysis, each supported by a single pivotal trial. Comparing BICR- and investigator-assessed ORRs in a pooled analysis did not identify any significant difference between the two assessments overall: OR = 0.98 (95% CI: 0.87-1.11), p = 0.75, and I2 = 0%. The correlation analysis also revealed a high level of concordance between BICR- and investigator-assessed ORRs, with r = 0.96 (p < 0.05).

Conclusions: This study found no evidence of evaluation bias in the assessment of ORR among registrational trials supporting recent FDA approvals of anticancer agents for solid tumor indications.