Real-world evidence provides clinical insights into tissue-agnostic therapeutic approvals

Area of Science:

• Oncology
• Genomics
• Pharmacology

Background:

• The US Food and Drug Administration (FDA) increasingly approves tissue-agnostic therapies targeting specific tumor biomarkers.
• Understanding the clinical utility of these therapies across diverse cancer types is crucial due to their growing prevalence.

Purpose of the Study:

• To analyze the clinical benefit of FDA-approved tissue-agnostic therapies across various cancer types.
• To investigate the prevalence of key tissue-agnostic biomarkers and assess treatment outcomes.

Main Methods:

• Analysis of a large database (295,316 samples) of molecularly profiled tumors with clinical outcomes.
• Evaluation of tissue-agnostic indications including high tumor mutational burden (TMB-High), mismatch repair deficiency (MSI-High/MMRd), BRAF^V600E mutations, and NTRK/RET fusions.

Main Results:

• 21.5% of tumors met criteria for at least one tissue-agnostic indication; 5.4% lacked cancer-specific indications.
• Low uptake of targeted therapies for rare NTRK fusions was observed.
• Significant variations in pembrolizumab outcomes for TMB-High and MSI-High/MMRd tumors across cancer types were identified.
• Clinical benefits were noted in tumor types and drug classes beyond pivotal trial investigations.

Conclusions:

• Treatment effects of tissue-agnostic therapies are not uniformly applicable across all tumor types.
• Findings suggest potential for expanding therapeutic strategies for patients with specific tissue-agnostic biomarkers.
• Further research is warranted to optimize the use of these targeted therapies.