A cross-sectional study of the FDA approved indications and supporting pivotal trials of small-molecular kinase inhibitors in cancer therapies with the biomarker of cancer driver gene.

Cancer precision medicine with biomarker of cancer driver gene (CDG) has been achieved by many small-molecular kinase inhibitors (SMKIs) approved by the US Food and Drug Administration (FDA). Publicly available FDA documents were collected for all SMKI cancer drugs approved between January 2001 and December 2021. Characteristics of indication and pivotal trial were compared. We identified 62 SMKI cancer drugs with 150 indications approved by the FDA between 2001 and 2021. Of these, 55 indications (36.7%) were CDG biomarker-directed. There was a significant increase of 20.5% per year in the number of approved CDG biomarker-directed indications. CDG biomarker-directed indications were associated with significantly higher odds in receiving accelerated approval (odds ratio [OR] = 2.728; 95% CI, 1.246-5.973; P = .012), designating orphan drug (OR = 3.952; 95% CI, 1.758-8.883; P < .001), initial submission of the application (OR = 2.246; 95% CI, 1.063-4.746; P = .034) and in solid cancer (OR = 7.613; 95% CI, 2.958-19.590; P < .001), and were associated with significantly lower odds in using randomized controlled trials (RCTs) (OR = 0.103; 95% CI, 0.032-0.338; P < .001) with less number of entered patients (OR = 0.998; 95% CI, 0.997-1.000; P = .048). The number of CDG biomarker-directed indications in approved SMKIs increased significantly in past two decades, with higher proportion of approvals using special expedited development and approval pathways at the FDA. Further RCTs should be conducted to prove long-term effectiveness and safety.