CASE REPORT article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Sequential Targeted Therapy in Synchronous Dual-Primary Lung Adenocarcinomas with EGFR and RET Alterations: A 5-Year Follow-Up Case Report
Provisionally accepted
- 1No 2 People's Hospital of Fuyang City, Fuyang, China
- 2Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 3Anhui Chest Hospital, Hefei, China
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With the increasing detection of multiple primary pulmonary nodules, accurately distinguishing between multiple primary lung cancers and intrapulmonary metastasis is crucial for diagnosis and treatment. We herein report a case of a 71-year-old female with bilateral multiple primary lung adenocarcinomas, in which separate lesions harbored an EGFR 19del mutation and a RET fusion gene, demonstrating intratumoral genetic heterogeneity. The patient was successively treated with an EGFR-TKI, chemotherapy, and the RET inhibitor pralsetinib, the latter of which maintained a response for over three years. 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.
Keywords: Anlotinib, dual-primary lung adenocarcinoma, EGFR mutation, Intratumoral heterogeneity, Pralsetinib, RET fusion
Received: 17 Dec 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Niu, Yang, Teng, Han and WANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ming-feng Han
DI-MING WANG
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