摘要：For oncology drugs that were approved by the US Food and Drug Administration (FDA) and required pharmacogenomic biomarker testing, we describe 1) the use of enrichment (biomarker-positive patients) and a randomized controlled design by pre-approval trials and 2) the treatment-by-biomarker interaction. From the 137 drugs included in the FDA table, we selected the 22 oncology drugs with required genetic testing in their labels. These drugs corresponded to 35 approvals supported by 80 clinical studies included in the FDA medical officer reviews of efficacy. For two thirds of approvals (24/35, 69%), all clinical studies were restricted to biomarker-positive patients (enriched). Among the 11 remaining approvals with at least one non-enriched trial, for five approvals, the non-enriched studies were non-randomized. The treatment-by-biomarker interaction was statistically significant for three approvals and missing for two. Among the six approvals with a non-enriched randomized controlled trial, three featured a statistically significant treatment-by-biomarker interaction (p < 0.10), for an enhanced treatment effect in the biomarker-positive subgroup. For two thirds of FDA approvals of anticancer agents, the requirement for predictive biomarker testing was based on clinical development restricted to biomarker-positive patients. We found only few cases with clinical evidence that biomarker-negative patients would not benefit from treatment.
