Metastatic pulmonary carcinoids with EML4-ALK fusion response to ALK inhibitors: two case reports and review of literature

Xi Lei, Shuai Zhu, Dian Ren, Fan Ren, Tong Li, Ning Zhou, Shuo Li, Tao Shi, Lingling Zu, Zuoqing Song, Justyna Chalubinska-Fendler, Marc G. Denis, Eric H. Bernicker, Vincent Thomas de Montpréville, Richeng Jiang, Song Xu

Research output: Contribution to journalArticlepeer-review


Background: Pulmonary carcinoids (PC), including typical (TC) and atypical carcinoids (AC), are low-grade neuroendocrine tumors (NETs) which account for 1–5% of all lung tumors. Due to the low prevalence of PC and extreme rarity of anaplastic lymphoma kinase (ALK) rearrangements in patients with PC, the advances in targeted therapy development in PC are still limited and there is no standard treatment. Even though in patients with PC harboring ALK rearrangements there is a room for a success in targeted therapy. To our knowledge, case 1 was the first report to detect ALK gene p.I1171N mutation after taking alectinib and sensitive to ceritinib in patients with atypical carcinoid. Case Description: Herein, we report the cases of 2 non-smoking patients, 51 year-old female with tumor in left lower lobe and 49 year-old female with tumor in right upper lobe, both with metastatic PC who harbored EML4-ALK fusion and were sensitive to small-molecule ALK inhibitors. The first patient initially received alectinib, then therapy was switched to ceritinib after developing drug resistance due to the missense mutation of ALK gene p.I1171N mutation in exon 22 detected by next-generation sequencing (NGS), and finally died of intracranial disease progression. The second patient also received alectinib, and her treatment is currently ongoing with good effect and tolerance. After conducting comprehensive review of literature, we found that 14 lung NETs with ALK rearrangements have been reported to date. The clinical outcome was partial response for 6 NETs patients and 5 patients exhibited stable disease after treatment with ALK inhibitors. Conclusions: According to the effectiveness of ALK inhibitors in our cases and previous articles, we recommend alectinib for the first-line treatment of metastatic PC with EML4-ALK fusion and highlight the need for molecular profiling of metastatic lung NETs patients and that ALK inhibitors are feasible in the treatment for metastatic lung NETs patients with ALK rearrangements. Finally, further studies to assess the real prevalence of ALK gene fusions and their spectrum of sensitivity to different ALK inhibitors are needed in larger cohorts.

Original languageEnglish (US)
Pages (from-to)1176-1184
Number of pages9
JournalTranslational Lung Cancer Research
Issue number6
StatePublished - Jun 2022


  • ALK rearrangement
  • alectinib
  • case report
  • lung neuroendocrine tumors (lung NETs)
  • pulmonary carcinoids (PC)

ASJC Scopus subject areas

  • Oncology


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