FDA Approvals of Oncology Drugs for Tissue-Agnostic Indications.

Abstract

The development of molecularly targeted oncology drugs for tissue-agnostic indications represents a new paradigm, but marketing authorization may carry additional risks due to uncertainties about extrapolating drug safety and efficacy, and biomarker test accuracy, to unstudied tumor types. To determine tumor types represented and method of mutation identification in trials supporting the US Food and Drug Administration (FDA) approvals of tissue-agnostic drugs, and to describe post-marketing requirements and commitments (PMRs/PMCs) issued for studies to evaluate additional tumor types and to validate companion diagnostic devices. For each tissue-agnostic drug approval identified via the FDA's Hematology/Oncology Approvals and Safety Notifications website, prescribing information, approval packages, and letters were retrieved from the Drugs@FDA website. Characteristics of approvals, details of supporting trials, and PMRs/PMCs for clinical trials and diagnostic tests were extracted. Six drugs were approved for seven tissue-agnostic indications between 2017 and 2022, with 9-15 different tumor types represented in trials supporting approvals. Only one approval prospectively utilized a commercial assay to identify the molecular alteration of interest in tumor samples. All seven approvals were issued PMRs for trials with additional tumor types, and six of seven were issued PMCs for studies to support labeling for companion diagnostic devices. The number of patients and cancer subtypes in trials supporting tissue-agnostic oncology drug approvals varied by mutation. Most drug approvals did not have concurrent approval of a diagnostic test. Post-marketing studies play a critical role in confirming clinical benefit and ensuring companion diagnostic device performance across a broader range of tumor types.