The Utility of Tissue-Agnostic Drugs in Lung Cancer Treatment

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Tissue-agnostic therapies target molecular alterations, not tumor site, and have FDA approval since 2017.
• Lung cancer is the leading cause of cancer-related deaths globally.
• Targetable genetic alterations are present in a subset of lung cancer patients.

Purpose of the Study:

• To evaluate the efficacy and safety of FDA-approved tissue-agnostic therapies in lung cancer patients with targetable genetic alterations.
• To review current evidence on specific tissue-agnostic drugs for NTRK gene fusions, BRAF V600E mutation, and RET fusions in lung cancer.

Main Methods:

• Systematic review of clinical trials and available data on FDA-approved tissue-agnostic therapies.
• Analysis of efficacy and safety data, including treatment-related adverse events.
• Evaluation of study limitations such as sample size and control group absence.

Main Results:

• Tissue-agnostic therapies demonstrate potential for treating lung cancer with NTRK gene fusions (larotrectinib, entrectinib, repotrectinib), BRAF V600E mutation (dabrafenib and trametinib), and RET fusions (selpercatinib).
• Rates of grade 3 or higher treatment-related adverse events varied widely, from 10% to 59.7%.
• Data are limited by small sample sizes (4-247 participants per cohort) and lack of control groups.

Conclusions:

• FDA-approved tissue-agnostic therapies show promise for specific molecularly defined subsets of lung cancer.
• Larger, controlled clinical trials and real-world data are necessary to confirm efficacy and safety.
• Further research will inform the broader clinical application of these targeted treatments in lung cancer.