RET fusion

P2, N=32, Not yet recruiting, University of Washington | Initiation date: Jun 2026 --> Sep 2026

This case demonstrates that for selected patients with advanced lung adenocarcinoma harboring a CCDC6-RET fusion and oligometastatic disease, initial systemic therapy with selpercatinib followed by local consolidative surgery is a feasible multimodal strategy. This is not a routine recommendation for stage IV lung cancer but requires individualized decision-making after multidisciplinary discussion in specific oligometastatic cases.

Selpercatinib, a RET inhibitor, is covered by insurance for all solid tumors that are positive for the RET fusion gene...In other solid tumors, positivity is less than 0.5%. However, if positive, treatment is expected to be effective, so it is desirable to actively perform cancer gene panel testing.

The patient did not respond to gemcitabine and cisplatin-based systemic chemotherapy. Selpercatinib, a selective inhibitor of receptor tyrosine kinase RET, blocks RET kinase activity by binding to its adenosine triphosphate-binding site, thus preventing the kinase from phosphorylating substrates and halting oncogenic signaling. The patient was treated with selpercatinib, which produced a durable response lasting over 15 months in this chemotherapy-refractory patient, highlighting the efficacy of selpercatinib in HOOK3-RET fusion-positive pancreatic cancer.

Continuous genomic monitoring is essential for identifying resistance mechanisms and guiding precision therapy. Future studies should explore the impact of different fusion partners on tumor behavior and therapeutic response.

Results from LIBRETTO-432 demonstrate that adjuvant selpercatinib yields a substantial improvement in event-free survival for patients with early-stage RET fusion-positive non-small cell lung cancer. Experts say the findings establish selpercatinib as a new standard of care for this rare disease, although questions remain over identifying patients and access to screening.

Among patients with stage II or IIIA RET fusion-positive NSCLC, event-free survival was significantly longer with adjuvant selpercatinib than with placebo. (Funded by Lilly; LIBRETTO-432 ClinicalTrials.gov number, NCT04819100.).

Demonstrated analytical and clinical performance of F1CDx led to the pan-tumor approvals from the U.S. Food and Drug Administration (FDA) in 2023 and the Japan Ministry of Health, Labour and Welfare (MHLW) in 2024 of F1CDx to identify RET fusions in solid tumor patients for treatment with selpercatinib. F1CDx is an accurate, reliable, FDA- and MHLW-approved method for the pan-tumor identification of RET fusions for treatment with selpercatinib.

In CRC, TAT was 4.1, 5.3, and 10.2; QNS 0%, 0%, 7.5%; detection 63.9%, 62.5%, and 57.1%. OPA provides faster TAT and lower QNS rates with comparable detection of actionable alterations, supporting its use for community-based molecular testing in NSCLC and CRC.

We discuss how these biological differences influence treatment response and their implications for future drug development and clinical trial design. Addressing these biological and clinical complexities will be essential to optimize the use of tumor-agnostic therapies across diverse cancer types.

The observation is hypothesis-generating rather than proof of sensitivity. This case provides a reference for precision treatment strategies after resistance to RET inhibitors.