IPM Take
Tissue-agnostic approvals are supposed to liberate treatment from tumour-site silos. But they only work if molecular testing escapes the same silos. RET fusions are rare. That is exactly why broad testing, clean reporting and referral discipline matter. Otherwise, tissue-agnostic medicine becomes available only to patients lucky enough to be tested in the right centre.
Executive Summary
The FDA granted traditional approval to selpercatinib for adults and paediatric patients aged two years and older with locally advanced or metastatic solid tumours with a RET gene fusion, detected by an FDA-approved test, after progression on prior systemic treatment or where no satisfactory alternatives exist. Selpercatinib had previously received accelerated approval for this tissue-agnostic indication in adults in 2022 and in paediatric patients aged two years and older in 2024. In 75 patients with RET fusion-positive tumours other than NSCLC and thyroid cancer in LIBRETTO-001, the overall response rate was 47%, with median duration of response of 24.5 months.
Why it matters
- Patients / advocates: Rare actionable fusions can cut across tumour types, but patients only benefit if they are tested.
- Diagnostics / pathology: Broad molecular profiling becomes the gateway to treatment, not an optional refinement.
- Clinicians: Tumour-site habits must not block treatment decisions driven by actionable genomic alterations.
- Regulators: Traditional approval confirms clinical benefit in a tissue-agnostic precision setting.
Tissue-agnostic oncology sounds clean in regulatory language. In real life, it is messy.
The FDA’s traditional approval of selpercatinib for RET fusion-positive solid tumours is a serious precision-oncology milestone. It applies across adult and paediatric patients aged two years and older, across locally advanced or metastatic solid tumours, and across tumour types where the RET fusion, not the organ of origin, is the defining feature.
That is the promise. The system problem is that rare fusions do not announce themselves.
In LIBRETTO-001, the FDA evaluated efficacy in 75 patients with RET fusion-positive tumours other than NSCLC and thyroid cancer. The overall response rate was 47%, and median duration of response was 24.5 months. Responses were seen across tumour types including colorectal cancer, pancreatic adenocarcinoma, salivary cancer, soft-tissue sarcoma, cholangiocarcinoma, breast cancer, ovarian cancer and neuroendocrine tumours.
This is why single-tumour thinking is no longer enough. A patient with pancreatic cancer, cholangiocarcinoma or sarcoma may carry an alteration that points toward a therapy approved beyond the original tumour-site categories. But if testing is narrow, late or unavailable, that patient will never enter the tissue-agnostic pathway.
The paediatric dimension matters too. The FDA notes supportive efficacy data in LIBRETTO-121, including responses in congenital infantile fibrosarcoma and spindle cell sarcoma, as well as RET fusion-positive thyroid cancer. Precision oncology is not only an adult metastatic-cancer story. It is increasingly a life-course testing story.
But no one should pretend the approval solves access by itself. Broad profiling still depends on reimbursement, tissue availability, lab capacity, report clarity, clinician confidence and referral routes to specialists who can interpret rare findings.
The medicine is tissue-agnostic. The health system is not there yet.
