STRN-ALK Fusion in a Case of Malignant Peritoneal Mesothelioma: Mixed Response to Crizotinib, Mode of Resistance, and Brigatinib Sequential Therapy

Our plain-English summary of STRN-ALK Fusion in a Case of Malignant Peritoneal Mesothelioma: Mixed Response to Crizotinib, Mode of Resistance, and Brigatinib Sequential Therapy, by V. Gerthofer, A. Scheiter, F. Lüke, et al (JCO Precision Oncology, 2021).

The study

• Authors: V. Gerthofer, A. Scheiter, F. Lüke, F. Keil, K. Utpatel, L.M. Pöhmerer, J. Seitz, C. Niessen, A. Ignatov, W. Dietmaier, D.F. Calvisi, M. Evert, O. Ortmann, S. Seitz
• Journal: JCO Precision Oncology
• Published: 2021;5
• Type of article: Case report
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

In plain English

This case report described a 24-year-old woman seen in April 2019 with lower abdominal pain and a 16 cm pelvic tumor. The tumor was first diagnosed as ovarian carcinoma. After genetic testing, the diagnosis was revised to biphasic malignant peritoneal mesothelioma. The article does not mention asbestos or any other exposure. Testing found an STRN-ALK gene fusion. After surgery and chemotherapy, she began the ALK-targeting drug crizotinib in December 2019. Her pain eased, and a scan two months later showed a partial response with tumor shrinkage at most sites. However, a new 9 × 4 cm pelvic lesion appeared, and liver metastases followed in April 2020. A June 2020 biopsy of an abdominal-wall metastasis found a secondary ALK mutation, L1196M, previously linked to crizotinib resistance in lung cancer. The drug brigatinib, started in July 2020, shrank several metastases, but new liver and spleen metastases appeared. She developed severe high blood sugar, which was attributed to brigatinib, and a gallbladder infection. She died in September 2020. The authors concluded that the case underlines the benefit of molecular testing in this disease.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (single patient)
• Who was studied: One 24-year-old woman who presented in April 2019 with lower abdominal pain, deep vein thrombosis and weight loss, and had a 16 cm pelvic tumor
• Exposure: The article does not report asbestos or any other environmental or occupational exposure. It concerns treatment of an STRN-ALK fusion-positive malignant peritoneal mesothelioma with two ALK inhibitors: crizotinib at 250 mg twice daily, then brigatinib at 90 mg once daily for 7 days followed by 180 mg once daily.
• Main results:
  • The tumor was initially diagnosed as high-grade serous ovarian carcinoma. The diagnosis was later revised to biphasic malignant peritoneal mesothelioma after unexpected next-generation sequencing results.
  • Sequencing of a November 2019 biopsy found an STRN-ALK fusion. FISH showed a positive break-apart pattern in 68% of tumor cells, and ALK immunohistochemistry was strongly positive.
  • A CT scan 2 months after starting crizotinib showed a partial response, with pronounced tumor shrinkage at most tumor locations. A new 9 × 4 cm pelvic lesion then appeared, causing urinary flow obstruction.
  • Liver metastases occurred in April 2020, and the disease progressed further. A June 2020 biopsy of the progressing abdominal wall metastasis found a secondary ALK mutation, p.L1196M, which has previously been associated with crizotinib resistance in non-small-cell lung cancer. ALK downstream markers were equally strongly activated before and during crizotinib treatment.
  • Brigatinib was started in July 2020. An August 2020 CT showed a mixed response: the pelvic, parailiacal and biopsied abdominal wall metastases shrank, the pulmonary metastases stayed the same, and multiple new liver and spleen metastases appeared.
  • The patient developed severe hyperglycemia (CTCAE grade 4, 757 mg/dL at admission), which was attributed to brigatinib. She also had a gallbladder empyema and Clostridium difficile colitis, and she died in September 2020.
• The authors' conclusion: The authors concluded that, to their knowledge, this was the first description of an STRN-ALK fusion-positive malignant peritoneal mesothelioma treated sequentially with two ALK inhibitors. They said the case underlines the benefit of molecular testing in this disease and suggests that lessons learned from lung cancer may apply to it.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma.

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• Complete and durable response to crizotinib in a patient with malignant pleural mesothelioma harboring CD74-ROS1 fusion — X. Xie, M. You, et al. (2022)
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