A case of multiple primary lung adenocarcinoma with a CD74‐NRG1 fusion protein and HER2 mutation benefit from combined target therapy

Neuregulin 1 (NRG1) gene fusion is a rare oncogenic driver gene in multiple tumor types, leading to the activation of the epidermal growth factor receptor (ErbB)‐mediated pathway. Therefore, afatinib, a pan‐ErbB family inhibitor, may be a therapeutic candidate for NRG1 fusion‐driven tumors. In this case, we report a multiple primary lung adenocarcinoma patient harboring the CD74‐NRG1 fusion, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (ERBB2) mutation simultaneously. The patient received afatinib and pyrotinib combination therapy and showed a significant treatment response with a progression‐free survival of 5 months. Our case further supports the use of targeted therapy for NRG1 fusion‐positive non‐small‐cell lung cancer. Fig 1A shows the course of treatment for the patient in this case report. The patient underwent video‐assisted thoracoscopic (VATS) right upper lobectomy with mediastinal lymph node dissection in November 2020. And then she received 2 cycles of pemetrexed and carboplatin from January 2021 to February 2021. Because the needle biopsy of the left lower lobe lesion showed adenocarcinoma, she underwent Cyberknife treatment in June 2021. After the diagnosis of stage IV lung adenocarcinoma with pleural metastasis, she was treated with of atezolizumab plus albumin‐bound paclitaxel and carboplatin for 2 cycles from August 2021 to September 2021. As the brain MRI suggested multiple brain metastasis in October 2021, the patient was subsequently treated with a combined regimen of afatinib and pyrotinib from October 2021. Meanwhile, she was treated with whole‐brain radiotherapy for brain metastasis from November 2021 to December 2021. Figure 1B shows the CT images of the left lower lobe lesion and left pleural effusion at baseline before the start of chemoimmunotherapy (2021‐8), at baseline before the start of targeted therapy (2021‐10), at week 4 after targeted therapy (2021‐11), at week 12 after targeted therapy (2022‐3) respectively.