Precision medicine becomes reality-tumor type-agnostic therapy

Area of Science:

• Oncology
• Precision Medicine
• Molecular Biology

Background:

• Two major breakthroughs in precision oncology occurred in 2017 with approvals for anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs).
• These approvals marked a shift towards biomarker-based cancer treatment, establishing a precedent for tumor type-agnostic therapy.
• Larotrectinib, a TRK inhibitor, also demonstrated significant efficacy in solid tumors with NTRK-fusion proteins.

Purpose of the Study:

• To highlight the emergence of tumor type-agnostic therapies in precision medicine.
• To discuss the shared characteristics and implications of anti-PD-1 mAbs and TRK-targeting therapies.
• To emphasize the impact of genetic analysis tools on the clinical practice of cancer treatment.

Main Methods:

• Review of regulatory approvals for pembrolizumab and nivolumab for MSI-H/dMMR tumors.
• Analysis of clinical trial data for larotrectinib in NTRK-fusion positive solid tumors.
• Discussion of common features including biomarker-based patient selection, high clinical efficacy, durable responses, and parallel adult/pediatric development.

Main Results:

• Pembrolizumab and nivolumab received accelerated approvals for MSI-H/dMMR solid tumors and metastatic colorectal cancer, respectively.
• Larotrectinib showed high overall response rates (ORR) in adult and pediatric patients with NTRK-fusion positive solid tumors.
• Both anti-PD-1 mAbs and TRK inhibitors demonstrated biomarker-driven efficacy, durable responses, and applicability across multiple tumor types.

Conclusions:

• Tumor type-agnostic therapy, driven by biomarkers like MSI-H/dMMR and NTRK-fusions, has become a reality in oncology.
• These targeted therapies offer high efficacy and durable responses in well-defined patient populations.
• The advancement of precision medicine necessitates adjustments in drug development and clinical practice to accommodate these new treatment paradigms.