• Hongbiao Wang, Sujuan Zhu, Zhifeng Li, Xiaofang Qi, Liwen Zhang, Leiyu Ke, and Yingcheng Lin.
• Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
• Medicine (Baltimore). 2022 Sep 2; 101 (35): e30316.

RationaleA remarkable concurrence of an EGFR mutation and an EML4-ALK fusion (double positive) occasionally occurs within a narrow number of patients. Previous studies using targeted therapy on EGFR/ALK co-mutated patients have commonly focused on single tyrosine kinase inhibitors (TKIs) or on the sequential use of EGFR-TKIs and ALK-TKIs. At present, no consensus exists regarding the treatment of patients with double positive mutations. The effectiveness of precision therapy also remains unknown.Patient ConcernsA 53-year-old female non-smoker who described recurrent coughing and blood in her sputum over a month-long interval was examined at a local hospital.DiagnosisUsing computed tomography (CT) and positron emission tomography CT (PET-CT), the patient was diagnosed with Stage IVb lung adenocarcinoma (T4N3M1).InterventionsThe patient had a novel ALK-RAB10 rearrangement identified using DNA sequencing, which, at the transcript level, was actually a canonical ALK fusion that caused a response to alectinib therapy.OutcomesThe patient has achieved partial remission (PR), with a progression free survival (PFS) of 16 months, and continues to benefit.LessonsOur results may indicate differential sensitivities to TKIs in patients harboring an EGFR mutation and an ALK rearrangement. Our patient's response to alectinib, instead of to EGFR-TKIs, may lead to an expanded list of alectinib beneficiaries who have rare gene co-alterations in lung adenocarcinoma.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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