(340) Coverage fragmentation and diagnostic access barriers in U.S. payer policies for tumor-agnostic oncology: A systematic review of NTRK-, RET-, and MSI-H–based therapies

Background: : Tumor-agnostic therapies are approved based on molecular alterations rather than tumor origin. Between 2017 and 2021, the FDA approved TRK inhibitors (larotrectinib, entrectinib), RET inhibitors (selpercatinib, pralsetinib), and immunotherapies for mismatch repair deficient (MSI-H) tumors (pembrolizumab, dostarlimab). These therapies span a range of solid tumors, including rare and pediatric cancers. However, payer policies have not consistently kept pace with regulatory approvals, especially in diagnostic reimbursement and access for underrepresented populations.

Objective: : To evaluate how U.S. payers, including commercial insurers, Medicaid programs, and Medicare contractors, define coverage for tumor-agnostic therapies, with focus on biomarker testing, pediatric eligibility, prior authorization, and reimbursement for diagnostics.

Methods: : A systematic review was conducted using PRISMA 2020 guidelines. Sources included PubMed, Embase, CMS.gov, state Medicaid portals, Medicare contractor websites, and commercial payer policy databases. From 843 records (2018 to 2025), 92 full texts were reviewed and 27 met inclusion. Including 14 commercial policies, 9 Medicaid documents, and 4 Medicare determinations. Two reviewers independently extracted and cross-verified data using a standardized abstraction tool. Discrepancies were resolved by consensus. Findings were synthesized by payer type.

Results: : Eighteen policies addressed tumor-agnostic therapies: six for NTRK inhibitors, five for RET inhibitors, and seven for MSI-H immunotherapies. All required biomarker confirmation. Eleven recognized next-generation sequencing (NGS) as clinically appropriate. Only three of nine Medicaid programs provided NGS reimbursement guidance. Pediatric coverage appeared in all NTRK policies but only one RET policy. Pralsetinib remained limited to tumor-specific indications. Rare tumors and histologies not cited in NCCN or compendia guidelines were inconsistently addressed. Policy updates lagged FDA approvals by six to 24 months. Authorization criteria varied. Diagnostic workflows often began with immunohistochemistry, then confirmatory NGS. Reimbursement for genomic profiling was inconsistent.

Conclusions: : Coverage of tumor-agnostic therapies remains fragmented. Inconsistent diagnostic reimbursement, limited pediatric inclusion, and delayed policy updates hinder access. Aligning payer criteria with clinical evidence and regulatory approvals is essential. Targeted reforms may expand access to precision oncology.

Sponsorship:: None