A real-world study of RET fusion in patients with solid tumor.

e20678 Background: RET activates downstream oncogenic signaling pathways such as RAS/MAPK, which regulates essential cellular processes. RET fusion is established actionable target in lung cancer, thyroid cancer, and other solid tumors. Their clinicopathological and molecular features, treatment patterns, and prognostic implications remain less characterized. Methods: This single-center retrospective cohort study included patients with RET fusion-positive solid tumors who were diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University between August 1, 2016, and May 1, 2025. Demographic, pathological, molecular, treatment, and follow-up data were collected from electronic medical records. Survival analysis was performed using the Kaplan–Meier method, with prognostic factors analyzed by Lasso-Cox and multivariable Cox proportional hazards models, and safety was evaluated according to CTCAE version 5.0. Results: The study enrolled 160 patients with RET fusion-positive solid tumors. The median age is 58 years, 56.3% are female, and 73.1% are never smokers. Lung cancer is the predominant primary site, with KIF5B being the most frequent fusion partner and TP53 the most common co-altered gene. The median overall survival (mOS) across tumor types: 48 months for lung cancer (n = 115), not reached for thyroid cancer (n = 21), and 20 months for gastrointestinal tumors (n = 9). In the lung cancer subgroup, baseline liver metastasis (HR 7.2, 95% CI 2.03-25.55, p < 0.05), regional lymph node metastasis (HR 5.7, 95% CI 1.74-18.51, p < 0.05), and adrenal metastasis (HR 9.9, 95% CI 2.85-35.09, p < 0.05) are independent risk factors for OS. Compared to chemotherapy, RET-TKIs exhibited longer PFS in both first-line (median PFS 11 vs. 14 months; HR 1.41, 95% CI 2.17-13.21) and second-line treatment (median PFS 4 vs. 8 months; HR 1.49, 95% CI 1.82-41.04). Among 55 patients treated with RET-TKIs, median PFS was 12 months, with significantly shorter PFS observed in those harboring co-occurring driver gene alterations (4 vs. 14 months, p < 0.05). No statistically significant differences in PFS were detected between selpercatinib and pralsetinib (13 vs. 12 months; p = 0.37), nor between first-line and subsequent-line administration (12 vs. 13 months, p = 0.91). RET-TKIs demonstrated favorable tolerability profiles: selpercatinib was primarily associated with edema, rash, and hypertension, while pralsetinib showed higher incidence of thrombocytopenia and hepatic dysfunction. Conclusions: RET fusion is frequently observed in younger, female, never-smoking patients with lung cancer. RET-TKIs demonstrated a trend toward superior efficacy compared to chemotherapy in the advanced cohort, with manageable safety profiles.