Premature phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma

Our plain-English summary of Premature phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma, by K. Watanabe, Y. Okuma, S. Kawai, et al (Thoracic Cancer, 2021).

The study

• Authors: K. Watanabe, Y. Okuma, S. Kawai, M. Nagamata, Y. Hosomi
• Journal: Thoracic Cancer
• Published: 2021;12(11):1668-1672
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next-generation anthracycline that is commonly used to treat lung cancer. Here, we conducted a phase II trial of this drug in patients with previously treated MPM.

Methods: Eligible patients with MPM having adequate organ function and a performance status of 0-2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m2 AMR on days 1-3 every three weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Median progression-free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events were evaluated as secondary endpoints.

Results: This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2-11.2) months, and the median OS was 9.1 (range, 6.2-22.0) months. The median number of treatment cycles was three (range, 2-11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia.

Conclusions: Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.

© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

In plain English

This single-center, open-label, single-arm phase II trial in Tokyo, Japan, tested amrubicin in people with malignant pleural mesothelioma that had progressed after platinum-based chemotherapy. Patients received 35 mg/m2 on days 1 to 3 of each three-week cycle. The trial planned 26 patients but stopped early because too few eligible patients enrolled. Of six patients enrolled between September 2013 and July 2018, five were treated and analyzed. All five were men with a history of asbestos exposure and smoking. No patient's tumor shrank enough to count as a response. The disease stayed stable in three patients and progressed in two. Median progression-free survival was 2.4 months and median overall survival was 9.1 months. Four patients had grade 3 or higher neutropenia, a drop in infection-fighting white blood cells. The results section reports one case of febrile neutropenia, but the article's abstract says there were none. There were no treatment-related deaths, and heart toxicity was not observed. The authors said the sample was too small to show efficacy. They concluded that amrubicin is a potential treatment option in later lines of chemotherapy.

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: Single-center, open-label, single-arm phase II clinical trial; planned sample size 26; stopped early for low accrual
• Who was studied: Patients with unresectable advanced malignant pleural mesothelioma whose disease had progressed after platinum plus pemetrexed, treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Japan. Six were enrolled from September 2013 to July 2018. One was not treated because the disease worsened, leaving five analyzed. All five were men with histories of asbestos exposure and smoking, median age 65 (range 49 to 76). Four had epithelioid disease and one had unknown pathology.
• Exposure: Treatment with amrubicin, an anthracycline chemotherapy drug, at 35 mg/m2 on days 1 to 3 every three weeks until tumor progression or unacceptable side effects, given as second-line treatment. Asbestos exposure was recorded only as a patient characteristic and was not the subject of study.
• Main results:
  • The trial was stopped early because there were not enough eligible patients.
  • Among the five treated patients, three had stable disease and two had progressive disease. There were no responders (objective response rate 0%). The disease control rate was 60%, with the interval printed as "90 confidence interval = 27.2–85.7".
  • Among the five treated patients, median progression-free survival was 2.4 months (range 1.2 to 11.2) and median overall survival was 9.1 months (range 6.2 to 22.0).
  • The median number of treatment cycles was three (range 2 to 11). Treatment ended because of disease progression in four patients and, in one patient, the patient's preference related to grade 2 anorexia.
  • Nine side effects of grade 3 or higher occurred in four of the five patients. Grade 3 or higher neutropenia occurred in four patients. Leukopenia, anemia, thrombocytopenia and febrile neutropenia each occurred in one patient. The one non-blood side effect of this severity was dizziness.
  • The results section reports febrile neutropenia of grade 3 or higher in one patient, and one patient needed a dose reduction because of febrile neutropenia. This contradicts the article's abstract, which says there were no cases of febrile neutropenia.
  • There were no treatment-related deaths, and the cardiac toxicities often seen with anthracyclines were not observed.
• The authors' conclusion: The authors concluded that three patients had stable disease on amrubicin alone. In their view, the data suggested amrubicin is a potential treatment option for malignant pleural mesothelioma in later lines of chemotherapy. They also noted that the result was not statistically significant.
• Limitations the authors state:
  • The sample size was too small to show efficacy, and there were no responders.
  • Most patients had epithelioid mesothelioma; no sarcomatoid or biphasic cases were enrolled.
  • The trial was run at a single institution.
  • Anthracycline-based chemotherapy may not be a sufficient treatment option now that immunotherapy is available for this disease.

Topics

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

Medical terms in this study, explained in our Lexicon: Palliative Care, Chemotherapy, Pleural Mesothelioma, Lung Cancer, Performance Status, Disease Progression, Pemetrexed (Alimta), Progression-Free Survival.

Related studies

• Amrubicin in previously treated patients with malignant pleural mesothelioma: A phase II study — T. Ikeda, S. Takemoto, et al. (2020)
• Phase 2 study of sorafenib in malignant mesothelioma previously treated with platinum-containing chemotherapy — S. Papa, S. Popat, et al. (2013)
• The role of "closed abdomen" hyperthermic intraperitoneal chemotherapy (HIPEC) in the palliative treatment of neoplastic ascites from peritoneal carcinomatosis: report of a single-center experience — L. Orgiano, F. Pani, et al. (2016)
• Combination of cisplatin and lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma: Report of two cases — Y. Metaxas, R. Cathomas, et al. (2016)
• A phase II trial of dovitinib in previously-treated advanced pleural mesothelioma: The Ontario Clinical Oncology Group — S.A. Laurie, D. Hao, et al. (2017)
• Quality of life of patients with end-stage peritoneal metastasis treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) — K. Odendahl, W. Solass, et al. (2015)

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