Lurbinectedin in Refractory Diffuse Malignant Peritoneal Mesothelioma: Report of Two Cases

Our plain-English summary of Lurbinectedin in Refractory Diffuse Malignant Peritoneal Mesothelioma: Report of Two Cases, by L. Gros, P. Szturz, A. Diciolla, et al (Frontiers in Oncology, 2021).

The study

• Authors: L. Gros, P. Szturz, A. Diciolla, V. Kirchner, S. Peters, N. Schaefer, M. Hubner, A. Digklia
• Journal: Frontiers in Oncology
• Published: 2021;11:704295
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is a malignancy of serosal membranes. Parietal pleura is the most common site, with peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. The prognosis is often very poor with median overall survival ranging from 6 to 18 months in patients who are not candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to non-resectable disease or comorbid conditions. For patients with resectable disease, CRS and HIPEC have become the standard of care. However, for patients with unresectable malignant mesothelioma there is unfortunately no effective systemic treatment beyond the first line. Based on the results of a recent phase II trial, lurbinectedin has clinical activity and acceptable toxicity in the second- and third-line treatment of malignant pleural mesothelioma. However, until present, no data have been available for patients with MPM and for patients who become refractory after multiple treatment lines. We report on two patients with metastatic MPM who achieved durable disease control of 10+ and 8 months with lurbinectedin in the fourth and fifth treatment line, respectively.

Copyright © 2021 Gros, Szturz, Diciolla, Kirchner, Peters, Schaefer, Hubner and Digklia.

In plain English

This article, published as a Perspective, described two men with diffuse malignant peritoneal mesothelioma (DMPM), a cancer of the lining of the abdomen. Both had epithelioid mesothelioma and received the drug lurbinectedin through a compassionate use program after earlier treatments had failed. The first man, aged 66 when diagnosed in 2014, started lurbinectedin as his fourth line of treatment in May 2020, at half the usual dose because of reduced kidney function. Scans at 3, 6 and 9 months showed overall reduced activity of his pleural and peritoneal lesions. At his last visit in March 2021 there were no signs of progression. The second man, aged 37 when diagnosed in 2016, had surgery with heated abdominal chemotherapy, relapsed, and received lurbinectedin as his fifth line at the standard dose. His disease progressed 8 months after starting, and he was still alive. Side effects in both were grade 1. The article did not describe either man's asbestos exposure. The authors said the patients' good general condition may partly explain the results. They concluded the cases suggest the drug's utility in DMPM but need confirmation in a well-designed prospective clinical 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: report of two cases (published as a Perspective article)
• Who was studied: two men with heavily pretreated diffuse malignant peritoneal mesothelioma of epithelioid histology, treated at Swiss hospitals: one aged 66 at diagnosis (October 2014), with atrial fibrillation and 40 pack-years of smoking; one aged 37 at diagnosis (February 2016), with no past medical history
• Exposure: Treatment with lurbinectedin given through a compassionate use program: 1.6 mg/m2 every three weeks in case 1 (reduced dose because of renal impairment) and 3.2 mg/m2 every three weeks in case 2. The patients' asbestos exposure was not reported.
• Main results:
  • Case 1 received a lurbinectedin dose reduced to 50% because of renal impairment
  • Case 1: scans at 3, 6 and 9 months showed overall metabolic regression of the pleural and peritoneal lesions
  • Case 1: no progression at the last visit in March 2021, and the patient continued treatment
  • Case 1 side effects were grade 1 asthenia, diarrhea and abdominal pain
  • Case 2: metabolic regression at 3 months, maintained at 6 months
  • Case 2: disease progressed 8 months after the first lurbinectedin dose
  • Case 2 was still alive without substantial clinical deterioration
  • Case 2 side effects were grade 1 asthenia and abdominal pain
• The authors' conclusion: The authors concluded that the durable response and good tolerance in these two cases suggest the utility of lurbinectedin in DMPM, but that this needs confirmation in a well-designed prospective clinical trial.
• Limitations the authors state:
  • The long survival may be partly explained by the patients' good general condition, a potentially non-aggressive histology, multiple treatment lines and the experience of the surgical team and hospital. The authors said the same factors may partly explain the response to lurbinectedin.
  • The findings need confirmation in a prospective clinical trial

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Mesothelioma, Parietal Pleura, Peritoneum, Prognosis, Median Overall Survival, Cytoreductive Surgery, HIPEC.

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