Therapies currently in Phase II trials for malignant pleural mesothelioma

Our plain-English summary of Therapies currently in Phase II trials for malignant pleural mesothelioma, by G. Pinton, A.G. Manente, D. Tavian, et al (Expert Opinion on Investigational Drugs, 2013).

The study

• Authors: G. Pinton, A.G. Manente, D. Tavian, L. Moro, L. Mutti
• Journal: Expert Opinion on Investigational Drugs
• Published: 2013;22(10):1255-63
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure, whose incidence will peak within the next years. Despite an overall low response rate, the current first-line therapy is represented by combined chemotherapy with cisplatin and antifolate. Moreover, there are no currently approved regimens for relapsed or refractory MPM. Therefore, it is clear how both preclinical and clinical researches aimed at identifying new therapeutic targets and testing them in early clinical settings are badly needed.

Areas Covered: The aim of this review is to summarize and critically comment the ongoing Phase II trials for MPM.

Expert Opinion: Over the past few years, there has been a significant endeavor of addressing the clinical research for MPM beyond the very modest results of chemotherapy. Nonetheless, our understanding is that the treatment of MPM should not be merely 'copied' from that of other much better studied tumors. In the light of recent results, studies toward the metabolic characteristics of this tumor are being progressively addressed. These evidences are disclosing a rather unusual model of malignancy, very likely to be more sensitive to novel 'MPM cells- and microenvironment-tailored' therapy addressing these characteristics rather than the sole cancer proliferation.

In plain English

This article was a review, not a new study. The authors summarized Phase II clinical trials for malignant pleural mesothelioma, a cancer they described as associated with asbestos exposure. Most were ongoing in 2013, and the authors said the dovitinib trial would soon begin. Citing earlier work, they noted that the median response rate to standard cisplatin and antifolate chemotherapy was only 30%. Their table listed ten agents in eleven trials. These included drugs that block growth signals or tumor blood vessels (such as cediranib and NGR-hTNF), immunotherapies (tremelimumab and two vaccines), a modified herpes virus and zoledronic acid. As a result, the review gave few trial results. It also described findings from other studies, such as a single-agent cediranib study by Garland and colleagues in which 9% of patients had an objective tumor response. The authors concluded that mesothelioma should not be treated like other tumors and that its metabolism and surroundings deserved more attention. They said immunotherapy looked promising, while calling their conclusions cautious.

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: Narrative review of Phase II clinical trials, ongoing or about to start, for malignant pleural mesothelioma, with the authors' expert opinion
• Who was studied: No new patients were studied. The review covered Phase II trials in patients with malignant pleural mesothelioma (MPM). Table 1 lists ten agents in eleven trials, with planned enrolment ranging from 12 to 180 patients per trial. One tremelimumab trial also included peritoneal mesothelioma.
• Exposure: Investigational treatments, not asbestos exposure. Growth factor receptor inhibitors and antiangiogenic agents: IMC-A12 (cixutumumab), dovitinib, cediranib, PF-03446962 and NGR-hTNF. Immunotherapies: tremelimumab, the TroVax vaccine and a WT1 vaccine. Others: the modified herpes simplex virus HSV1716 and Zometa (zoledronic acid).
• Main results:
  • Background cited from earlier work: for standard first-line chemotherapy (cisplatin with an antifolate), the median response rate is only 30%, and its effect on overall survival is described as negligible.
  • Earlier clinical trials of the EGFR inhibitors gefitinib and erlotinib, and of the PDGF receptor inhibitor imatinib, given as single agents, were described as having failed.
  • The Phase II trial of dovitinib as a single agent in advanced MPM had not yet started; the authors said it would soon begin.
  • In a single-agent cediranib study by Garland et al. (another study, not this one), 9% of patients had an objective tumor response, 34% had stable disease and 43% had progressive disease.
  • An ongoing Phase I/randomized Phase II trial was comparing cediranib with placebo, each combined with cisplatin and pemetrexed, in MPM patients not previously given chemotherapy. Table 1 lists 116 patients for this trial. The primary outcome is progression-free survival.
  • A randomized, double-blind Phase II trial of tremelimumab versus placebo (2:1 ratio) in unresectable pleural or peritoneal malignant mesothelioma planned to enrol approximately 180 subjects in multiple countries.
• The authors' conclusion: The authors concluded that MPM should not be treated as similar to other human tumors. They argued that its metabolism, its microenvironment and the differences between its subtypes need more attention. They also concluded that immunotherapy looks like a promising approach.
• Limitations the authors state:
  • The authors said their conclusions must be cautious because much work remains.
  • The authors noted that cultured MPM cells and mouse models do not account for the microenvironment in which the tumor develops in humans.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, First-line Therapy, Chemotherapy, Cisplatin, Antifolate.

Related studies

• Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma — A. Guazzelli, E. Bakker, et al. (2017)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial — M. Maio, A. Scherpereel, et al. (2017)
• Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107) — T. Jahan, L. Gu, et al. (2012)
• Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium — N.P. Campbell, R. Kunnavakkam, et al. (2012)
• A phase II clinical trial of the vascular disrupting agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma — A.K. Nowak, C. Brown, et al. (2013)

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