RET positive

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.).

Outcomes observed in the RECALIB-RET RW benchmark population reflect the limitations of non-selective RETi therapies in RET fusion-positive NSCLC, and reinforce the rationale for early use of targeted agents such as selpercatinib. Optimizing biomarker testing practices may enable earlier access to these therapies.

The patient was treated with selpercatinib, resulting in radiographic response and clearance of circulating RET-mutant DNA. She remains progression-free 10 months into therapy and the infant continues normal development. This is the first reported case of RET p.M918T-mutated neuroendocrine lung cancer with placental metastases diagnosed during pregnancy, highlighting the importance of molecular profiling and multidisciplinary care.

Pralsetinib and selpercatinib are novel, highly selective RET tyrosine kinase inhibitors (RET-TKIs). Given the low prevalence of RET gene alterations (＜5%), which are regarded as rare genetic mutations, clinical experience in the use pf RET-TKIs and and patient management remains limited. Base on the current status of adverse event management of RET-TKIs in China, and integrating the latest international evidence and clinical experience, the Chinese Medical Doctor Association Tumor Multidisciplinary Diagnosis and Treatment Professional Committee and the Shenzhen Medical Doctor Association Tumor Multidisciplinary Diagnosis and Treatment Professional Committee organized discussion among experts from medical oncology, respiratory medicine, radiation oncology, thoracic surgery, and other related disciplines to formulate this expert consensus on the management of adverse events of RET-TKIs.

Several multikinase blockers targeting RET have been approved by the FDA for the treatment of cancer: (i) vandetanib for medullary thyroid carcinoma and (ii) cabozantinib, lenvatinib, and sorafenib for differentiated thyroid cancer. Pralsetinib is a specific RET blocker that is FDA-approved for the treatment of medullary thyroid cancer, RET-fusion positive thyroid cancer and NSCLC. Selpercatinib is FDA-approved for the management of RET-mutant medullary thyroid cancer, RET-fusion-positive thyroid cancer, and other RET-fusion-positive solid tumors...Currently, the number of new cases of thyroid cancer bearing RET mutations or RET-fusion proteins is about 13,000 per year and the number of cases of RET-driven NSCLC range from about 2000-4000 per year in the United States. Inactivating RET mutations result in Hirschsprung disease, a congenital disorder leading to aganglionosis of the gastrointestinal tract.

The new discoveries of RET fusion partners were founded in NSCLC. In addition, the broad-panel NGS is essential for NSCLC patients to catch these rare/novel fusions that PCR or small panels might miss.

The validation of the NMA results could be assessed for progression-free survival of selpercatinib versus pembrolizumab + pemetrexed + platinum-based chemotherapy. Enabling the earlier assessment of single-arm trials, via pseudo comparator arms, will provide payers with greater confidence in anticipated treatment effects. In light of the joint clinical assessment, incorporation of single-arm trials within NMA facilitates the reporting of predicted treatment effects relative to multiple relevant comparators, which is important when considering the use of interventions for the global market.

P4, N=25, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center