P1/2, N=265, Recruiting, Ellipses Pharma | Trial completion date: Jun 2027 --> Mar 2028 | Trial primary completion date: Dec 2026 --> Mar 2027

The consistent cost-effectiveness results between pre-submission and post-submission phases support the potential of SEE to complement health technology assessment (HTA) and potentially inform earlier (conditional) reimbursement decisions for this single case study. However, future research should focus on refining SEE protocols for continued methodological development and validation to improve generalizability and applicability.

P3, N=120, Active, not recruiting, Shouyao Holdings (Beijing) Co. LTD | Recruiting --> Active, not recruiting

Resistance to RET inhibitors can be acquired through RET copy-number gain and secondary mutations as well as NF1 loss-mediated MAPK pathway activation. This mechanism of resistance can be overcome with dual inhibition of RET and downstream RAS/MAPK signaling, demonstrating clinical potential in RET-mutant MTC.

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.

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.).

Using two mouse studies modeling multi-organ metastases and breast tumor formation in the brain, we observed that RET inhibition significantly prevented the circulating tumor cells from forming brain metastases and suppressed the growth of intracranially implanted tumor cells. Together, our findings demonstrated that RET functions as a novel mediator of BCBM and that RET inhibitors showed promising efficacy for BCBM.