Case Report: Malignant peritoneal mesothelioma with TFG-ROS1 fusion responds to crizotinib

Our plain-English summary of Case Report: Malignant peritoneal mesothelioma with TFG-ROS1 fusion responds to crizotinib, by W. Ye, P. Li, C. Fu, et al (Frontiers in Oncology, 2025).

The study

• Authors: W. Ye, P. Li, C. Fu, T. Zhou
• Journal: Frontiers in Oncology
• Published: 2025;15:1617457
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type, and its molecular properties are poorly understood. In recent years, gene rearrangement has been found in a subset of MPMs. However, ROS1 rearrangement has not been previously reported in MPM.

Case Presentation: Here, we present the first case report of MPM with TFG-ROS1 rearrangement in a 56-year-old female with no history of asbestos exposure. The patient did not respond to immunotherapy but exhibited sensitivity to crizotinib with a progression-free survival (PFS) of 6 months. Importantly, we identified ROS1 p.K1991N as a potential acquired drug resistance mutation to crizotinib, suggesting that entrectinib may serve as a targeted therapy to overcome this resistance mechanism.

Conclusion: ROS1 rearrangement could potentially represent a novel driver mutation in MPM, especially in female adults. This case report illustrates the benefits of molecular detection in MPM and underscores the potential for lessons learned from other solid tumors to inform treatment strategies for rare diseases.

Copyright © 2025 Ye, Li, Fu and Zhou.

In plain English

This case report described one patient: a 56-year-old woman with malignant peritoneal mesothelioma (a cancer of the abdominal lining) who had no history of asbestos exposure. Tumor testing found a TFG-ROS1 gene fusion, which the authors said had not been reported before in this disease. She received one cycle of pembrolizumab with pemetrexed chemotherapy in March 2022 and then had grade 4 bone marrow suppression. She was next given crizotinib, and a CT scan after 1 week showed a partial response. Six months after starting crizotinib, the disease progressed, and testing found an acquired ROS1 p.K1991N mutation. The disease progressed on lorlatinib and kept worsening on entrectinib with local radiotherapy. Ceritinib was stopped when jaundice worsened during treatment, and cabozantinib because of bleeding and hypertension. She was discharged in a coma in June 2023. The authors concluded that ROS1 rearrangement could potentially be a new driver mutation in this disease, especially in women. They suggested entrectinib might overcome the K1991N resistance, although her condition deteriorated on entrectinib. They called for further sample analysis and a multicenter trial.

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 (a single patient)
• Who was studied: One 56-year-old woman with malignant peritoneal mesothelioma. She first came to a local hospital in January 2022 and was later transferred to the authors' hospital in Changzhou, China. She had a history of type 2 diabetes and cervical cancer surgery 10 years earlier.
• Exposure: No asbestos exposure was reported. The article studied a tumor carrying a TFG-ROS1 gene fusion and its treatment with crizotinib and other ROS1-targeted drugs.
• Main results:
  • The authors stated that ROS1 rearrangement had not previously been reported in malignant peritoneal mesothelioma.
  • Next-generation sequencing of the tumor confirmed a TFG-ROS1 fusion, with no other relevant findings.
  • After one cycle of pembrolizumab combined with pemetrexed chemotherapy, the patient had grade 4 bone marrow suppression.
  • On crizotinib (250 mg twice daily), a CT scan after 1 week showed a partial response.
  • During crizotinib treatment, her performance status (ECOG PS) improved from 3 to 1. The main adverse event reported was grade 2 gastrointestinal discomfort.
  • Six months after starting crizotinib, a CT scan on October 12, 2022 showed progression.
  • Testing of the pelvic mass at progression found the TFG-ROS1 rearrangement plus an acquired ROS1 p.K1991N mutation.
  • In January 2023, CT showed multiple masses in the abdomen and pelvis, some of them new. The authors interpreted this as acquired resistance to lorlatinib.
  • Her condition continued to deteriorate on entrectinib and local radiotherapy.
  • Repeat testing found new ROS1 point mutations, p.L2086F and p.S1986F. The p.K1991N mutation was no longer present.
  • Jaundice increased during ceritinib treatment, and the drug was stopped.
  • On cabozantinib, CT showed partial shrinkage of the abdominal mass after one week. The drug was then stopped because of bleeding and hypertension.
  • The patient was discharged from the hospital in a coma on June 27, 2023.
• The authors' conclusion: The authors concluded that ROS1 rearrangement could potentially be a new driver mutation in malignant peritoneal mesothelioma, especially in female adults. They also concluded that the case shows the benefits of molecular testing in this disease. They suggested that ROS1 p.K1991N caused resistance to crizotinib and that entrectinib may overcome it.
• Limitations the authors state:
  • The authors said further sample analysis is needed to validate the findings.
  • The authors said a multicenter trial is needed to show whether ROS1 inhibitors work in this disease, given its rarity.
  • The authors speculated that the female hormone (estrogen) environment favors ROS1 rearrangement, and said this needs experimental verification.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, ROS1, Asbestos Exposure, Immunotherapy, Progression-Free Survival, Targeted Therapy.

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