LUME-Meso: Design and Rationale of the Phase III Part of a Placebo-Controlled Study of Nintedanib and Pemetrexed/Cisplatin Followed by Maintenance Nintedanib in Patients With Unresectable Malignant Pleural Mesothelioma

Our plain-English summary of LUME-Meso: Design and Rationale of the Phase III Part of a Placebo-Controlled Study of Nintedanib and Pemetrexed/Cisplatin Followed by Maintenance Nintedanib in Patients With Unresectable Malignant Pleural Mesothelioma, by G.V. Scagliotti, R. Gaafar, A.K. Nowak, et al (Clinical Lung Cancer, 2017).

The study

• Authors: G.V. Scagliotti, R. Gaafar, A.K. Nowak, M. Reck, A.S. Tsao, J. van Meerbeeck, N.J. Vogelzang, T. Nakano, U. von Wangenheim, D. Velema, N. Morsli, S. Popat
• Journal: Clinical Lung Cancer
• Published: 2017;18(5):589-593
• Type of article: Randomized trial
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare but aggressive disease: median survival is 6 to 9 months if untreated. Standard first-line treatment for patients with unresectable MPM is cisplatin/pemetrexed, with a median overall survival (OS) of approximately 1 year. Improvements in first-line treatment options are needed. With the benefit of combining bevacizumab with standard therapy shown in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS), vascular endothelial growth factor (VEGF) pathway inhibition has gained renewed interest as a treatment approach. Nintedanib is an oral angiokinase inhibitor targeting multiple signaling pathways implicated in the pathogenesis of MPM, including the VEGF receptor. The phase III part of the international, phase II/III LUME-Meso study is evaluating the efficacy and safety of nintedanib plus pemetrexed/cisplatin in patients with unresectable epithelioid MPM. Originally, this was a double-blind, randomized, phase II exploratory study and was amended to include a confirmatory phase III part following the recommendation of an internal Data Monitoring Committee and review of phase II data. The phase III part plans to enroll 450 chemotherapy-naive patients, who will be randomized to receive pemetrexed/cisplatin on day 1 and nintedanib or placebo on days 2 to 21, for a maximum of 6 cycles. Patients without disease progression who are eligible to continue study treatment will receive maintenance treatment with nintedanib or placebo until disease progression or undue toxicity. The primary end point is progression-free survival; OS is the key secondary end point. The study will use an adaptive design, including an interim analysis to reassess the number of OS events required to ensure sufficient power for OS analysis. The study is currently enrolling patients.

Copyright © 2017 Elsevier Inc. All rights reserved.

In plain English

This article described the plan for the phase III part of LUME-Meso, a double-blind, randomised, placebo-controlled trial in patients with malignant pleural mesothelioma that could not be removed by surgery. It reported no treatment results from LUME-Meso itself. The phase III part planned to enrol 450 patients with epithelioid-type tumours. Patients were to receive up to 6 cycles of standard pemetrexed and cisplatin chemotherapy, plus either the oral drug nintedanib or a matching placebo. Patients whose disease had not progressed and who remained eligible would then continue nintedanib or placebo until clear progression, unmanageable side effects, withdrawal of consent or death. The investigator could allow treatment beyond progression if the patient seemed to benefit. The main measure was progression-free survival, and overall survival was the key secondary measure. Using phase II data, the authors chose 450 patients to give 90% power for progression-free survival. Overall survival would use an adaptive design because only 53% of survival events were available from phase II. The authors stated that the trial will determine whether adding nintedanib offers clinical benefit. Asbestos exposure was not studied.

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: Design and rationale article for the phase III part of a double-blind, randomised, multicentre, placebo-controlled, phase II/III drug trial. It reports no outcome results from this trial.
• Who was studied: Planned enrolment of 450 patients with unresectable malignant pleural mesothelioma of epithelioid histology only. The trial was still enrolling.
• Exposure: The study examined drug treatment, not asbestos exposure. Patients received up to 6 cycles of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on Day 1, plus nintedanib 200 mg twice daily or matched placebo on Days 2 to 21. Patients without disease progression who remained eligible then received maintenance nintedanib or placebo. Treatment beyond progression was allowed if the investigator judged the patient was benefiting.
• Main results:
  • Planning figure, not a treatment result: the phase III sample size of 450 patients was set to give 90% power to detect an improvement in progression-free survival.
  • Planning figure, not a treatment result: at the phase II primary analysis, 79% of progression-free survival events and only 53% of overall survival events were available. This was the reason for using an adaptive design for overall survival.
• The authors' conclusion: The authors stated that the trial will determine whether adding nintedanib to pemetrexed/cisplatin offers clinical benefit in progression-free survival (primary endpoint) and overall survival (key secondary endpoint).

Topics

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

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Cisplatin, Unresectable, Pleural Mesothelioma, Median Overall Survival, Bevacizumab, Mesothelioma, Epithelioid.

Related studies

• Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial — G.V. Scagliotti, R. Gaafar, et al. (2019)
• Phase I Trial of Cediranib in Combination with Cisplatin and Pemetrexed in Chemonaive Patients with Unresectable Malignant Pleural Mesothelioma (SWOG S0905) — A.S. Tsao, J. Moon, et al. (2017)
• Phase I trial of cisplatin, pemetrexed, and imatinib mesylate in chemonaive patients with unresectable malignant pleural mesothelioma — A.S. Tsao, N. Harun, et al. (2014)
• A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol — N. Fujimoto, K. Aoe, et al. (2018)
• 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)
• Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial — G.L. Ceresoli, J.G. Aerts, et al. (2019)

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