Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study

Our plain-English summary of Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study, by T. Nakano, K. Kuribayashi, M. Kondo, et al (Asia-Pacific Journal of Clinical Oncology, 2021).

The study

• Authors: T. Nakano, K. Kuribayashi, M. Kondo, M. Morise, Y. Tada, K. Hirano, M. Hayashi, M. Tanaka, M. Hirabayashi
• Journal: Asia-Pacific Journal of Clinical Oncology
• Published: 2021;17(3):264-272
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aims: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis and limited treatment options. Cisplatin plus pemetrexed is the only approved first-line treatment for patients with unresectable MPM. Recently, promising outcomes were observed with first-line bevacizumab combined with cisplatin/pemetrexed, leading to the recommendation of this regimen as a first-line treatment option for patients with MPM. Bevacizumab plus cisplatin/pemetrexed has been shown to be safe and effective in non-small cell lung cancer, however, there are no efficacy or safety data in Japanese patients with MPM treated with this regimen. We conducted a multicenter study to evaluate tolerability and safety for Japanese patients with chemotherapy-naïve, unresectable MPM.

Methods: Eligible patients (n = 7) received bevacizumab plus cisplatin/pemetrexed (up to six cycles), then single-agent bevacizumab until disease progression or onset of unacceptable adverse events (AEs), according to the 3+3 design analogy.

Results: One patient (14.3%) reported an AE (gastric ulcer) meeting tolerability criteria. All patients experienced gastrointestinal disorders, including nausea (grade 1/2 only, n = 6, 85.7%) and constipation (grade 1/2 only, n = 5, 71.4%). Five patients (71.4%) had grade 3 hypertension. Two patients discontinued treatment due to gastric ulcer (n = 1) and proteinuria (n = 1). At data cut-off, four patients had stable disease, two had partial response and one had non-complete response/non-progressive disease due to the absence of target lesions.

Conclusions: Bevacizumab plus cisplatin/pemetrexed then bevacizumab was well tolerated in Japanese patients with MPM.

© 2020 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.

In plain English

This was a small, single-arm study at four centers in Japan. It tested whether adding bevacizumab to the chemotherapy drugs cisplatin and pemetrexed (up to six cycles), then bevacizumab alone, was tolerable as a first treatment. The seven patients had malignant pleural mesothelioma that could not be removed by surgery. The study did not examine asbestos exposure. In the first treatment cycle, one of seven patients (14.3%) had a side effect meeting the study's tolerability criteria, a gastric ulcer. All seven patients had at least one side effect. Five (71.4%) had grade 3 high blood pressure, which the authors reported was managed with medication. There were no grade 4 or 5 side effects and no deaths. Two patients stopped treatment because of side effects: a gastric ulcer and protein in the urine. Four patients had stable disease and two had a partial response; one, who had no target lesions, had neither a complete response nor progression. The authors concluded the regimen was well tolerated in this small patient dataset. They noted that comparisons with other trials are difficult.

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-arm (no comparison group), multicenter study of a first-line treatment regimen; target sample size of six patients based on an analogy to a 3+3 design
• Who was studied: Seven Japanese patients from four centers with unresectable malignant pleural mesothelioma who had not had chemotherapy before. Median age was 66 (range 47–73); 4 were male and 3 female; 6 had epithelioid histology. Data cut-off was September 15, 2016 for tolerability and July 6, 2017 for safety and efficacy; enrollment dates were not given.
• Exposure: Not an asbestos exposure study. The exposure studied was drug treatment: bevacizumab plus cisplatin and pemetrexed every 3 weeks for up to six cycles (pemetrexed 500 mg/m2, cisplatin 75 mg/m2, bevacizumab 15 mg/kg), then bevacizumab 15 mg/kg alone every 3 weeks until disease progression or unacceptable side effects. One patient switched from cisplatin to carboplatin for cycles 5 and 6 because of reduced kidney function.
• Main results:
  • During the tolerability evaluation period (cycle 1), 1 of 7 patients (14.3%) had an adverse event meeting the tolerability criteria: a gastric ulcer.
  • All 7 patients had at least one adverse event of any grade; 74 adverse events were reported in total.
  • The most common gastrointestinal adverse events were nausea (6 of 7 patients, 85.7%) and constipation (5 of 7, 71.4%), any grade.
  • Five of 7 patients (71.4%) had grade 3 hypertension. The authors noted this compared with 23% of patients in the earlier MAPS trial. They reported it was manageable with antihypertensive medication, allowing patients to continue bevacizumab.
  • Other grade 3 adverse events (elevated amylase, elevated gamma-glutamyltransferase, hyponatremia, anemia and proteinuria) each occurred in one patient (14.3%). There were no grade 4 or 5 adverse events.
  • Two patients stopped treatment because of adverse events: one for a gastric ulcer and one for proteinuria. No deaths were reported.
  • At data cut-off, best responses among the 7 patients were: 4 stable disease, 2 partial response, and 1 non-complete response/non-progressive disease (because there were no target lesions).
  • Progression-free survival was 0.9, 2.7, 6.7 and 6.8 months for the four patients with stable disease. It was 10.4 and 11.1 months (censored, still on treatment) for the two with a partial response. Median progression-free survival was 6.8 months.
• The authors' conclusion: The authors concluded that bevacizumab plus cisplatin and pemetrexed, followed by bevacizumab maintenance, was well tolerated and had satisfactory efficacy in this small patient dataset. In their view this warrants its first-line use in Japanese patients with malignant pleural mesothelioma, based on the phase III study in France.
• Limitations the authors state:
  • The authors described the patient dataset as small.
  • The authors stated that comparing results across trials is difficult because of differences in study designs, assessment methods and patient populations.
  • Patients did not have gastroendoscopy before enrollment, so it is unknown whether the gastric ulcer was already present at baseline.

Topics

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

Medical terms in this study, explained in our Lexicon: Bevacizumab, Cisplatin, Pemetrexed (Alimta), Unresectable, Pleural Mesothelioma, Prognosis, Non-Small Cell Lung Cancer, Chemotherapy.

Related studies

• Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial — M. Zhan, H. Zheng, et al. (2017)
• Comparison of cisplatin plus pemetrexed and cisplatin plus gemcitabine for the treatment of malignant pleural mesothelioma in Japanese patients — T. Shukuya, T. Takahashi, et al. (2014)
• A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma — J.E. Dowell, F.R. Dunphy, et al. (2012)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)
• A feasibility study of induction pemetrexed plus cisplatin followed by pleurectomy/decortication aimed at macroscopic complete resection for malignant pleural mesothelioma — M. Shimokawa, S. Hasegawa, et al. (2013)
• First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma — E. Fujimoto, T. Kijima, et al. (2017)

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