RET positive

Given the current pricing, neither selpercatinib as a first-line therapy nor as a second-line therapy was deemed to be cost-effective compared with chemotherapy for advanced NSCLC patients with RET fusions. Further real-world studies of selpercatinib and development of health outcome estimate scales are needed to provide additional evidence for clinicians and health policy decision-makers.

The therapeutic strategy involved an immediate switch from rivaroxaban to therapeutic low-molecular-weight heparin (LMWH) and the initiation of dual targeted therapy with selpercatinib and tepotinib. Upon diagnosis of NBTE, a rapid oncologic work-up is warranted, as ongoing tumor progression is highly likely. This case questions the appropriateness of direct oral anticoagulants in patients with NBTE and active, progressive malignancy.

Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs, confirming previous findings with longer follow-up.

P2, N=124, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026

P3, N=291, Active, not recruiting, Loxo Oncology, Inc. | Trial completion date: Feb 2026 --> Nov 2027

Following the development of resistance, combination therapy with pralsetinib and anlotinib successfully achieved a partial response again. This case underscores the importance of comprehensive molecular testing across multiple lesions to guide precision therapy and provides clinical insights into RET fusion-positive lung cancer treatment and post-resistance combination strategies.

Furthermore, the review elaborates on the clinical efficacy of highly selective RET inhibitors (selpercatinib and pralsetinib), including their breakthroughs in pediatric patients and radioactive iodine-refractory cases. Primary and acquired resistance mechanisms (on-target mutations, bypass activation) and corresponding strategies (next-generation inhibitors, combination therapies) are also analyzed. By integrating recent advances in basic and clinical research, this review provides a comprehensive reference for the precision diagnosis and treatment, mechanistic investigation, and drug development for RET fusion-positive PTC.

P=N/A, N=25, Not yet recruiting, Fudan University

RET fusion-positive LUAD comprises biologically heterogeneous subsets defined by fusion partners. KIF5B-RET tend to occur at earlier stages, whereas non-KIF5B are more frequently associated with CDKN2A co-mutations and may derive greater benefit from selective RET inhibition. Immunochemotherapy demonstrates comparable efficacy regardless of fusion partner, highlighting the need for partner-specific therapeutic strategies in RET fusion-positive LUAD.

Herein, we present a clinical case of a patient with stage IIIA RET fusion-positive adenocarcinoma who received neoadjuvant nivolumab immunotherapy combined with nab-paclitaxel and carboplatin chemotherapy followed by surgery. The postoperative pathologic results revealed pathological complete response (pCR) and no residual viable tumor cells were observed in lymph nodes. This case validates the clinical activity of immunotherapy-chemotherapy in the neoadjuvant setting, providing a foundation for continued exploration in the treatment of early-stage RET fusion-positive NSCLC.

These findings provide new insights into the individualized treatment of RET + NSCLC patients and emphasize the importance of considering the overall health status of patients in treatment decisions.