Review on clinical trials of targeted treatments in malignant mesothelioma

Our plain-English summary of Review on clinical trials of targeted treatments in malignant mesothelioma, by J.N. Jakobsen, J.B. Sørensen (Cancer Chemotherapy and Pharmacology, 2011).

The study

• Authors: J.N. Jakobsen, J.B. Sørensen
• Journal: Cancer Chemotherapy and Pharmacology
• Published: 2011;68(1):1-15
• Type of article: Review
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all clinical trials evaluating the effect of targeted treatments in MM.

Methods: An extensive literature search was performed in January 2011 using pubmed and medline. No constraints on publication date were applied.

Results: Thirty-two trials exploring 17 different targeted agents in MM were found. Treatment in first- and second-line targeted agents induced response rates ranging from 0-14% and 0-16%, respectively. The tyrosine kinase inhibitor sunitinib induced partial response in 10% and stable disease in 66% of MPM patients as second-line treatment. A preliminary analysis of a phase II/III trial suggests that addition of bevacizumab to pemetrexed and cisplatin first-line treatment significantly improves disease control (CR + PR + SD) in the bevacizumab arm (73.5%) compared with treatment with pemetrexed and cisplatin without bevacizumab (43.2%) (P = 0.010). Another phase II trial did not observe any significant clinical benefit of adding of bevacizumab to gemcitabine and cisplatin.

Conclusions: Disease stabilization is reported in some patients with several targeted treatments and might be beneficial in subgroups of patients or in combination with classic chemotherapy. None of the hitherto explored targeted treatments can currently be recommended as standard treatment in MM.

In plain English

This article was a review, not a new study. The authors searched PubMed and Medline in January 2011 for clinical trials of targeted drug treatments in malignant mesothelioma, with no date limit. They found 32 trials testing 17 targeted agents. Response rates were 0–14% as first treatment and 0–16% as second-line treatment. Four single-drug imatinib trials had no responders; the text gave 94 patients in total, but the table's counts add to 82. In a second-line sunitinib trial of 53 enrolled patients, the response rate was 10% and 33 had stable disease, reported as 66%, a share that does not match 33 of 53. A preliminary analysis of one trial found disease control at 6 months in 25 of 34 patients (73.5%) given bevacizumab with pemetrexed and cisplatin, against 16 of 37 (43.2%) without it (P = 0.010). Another trial found no improved benefit from adding bevacizumab to gemcitabine and cisplatin. The authors concluded that no targeted treatment explored so far could be recommended as standard treatment, though some might help subgroups or work with 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: Literature review of clinical trials (phase I to III) of targeted treatments in malignant mesothelioma
• Who was studied: 32 published clinical trials of 17 targeted agents in malignant mesothelioma patients, mostly with malignant pleural mesothelioma. These included conference abstracts from ASCO 2009 and 2011. Ongoing trials were taken from clinicaltrials.gov.
• Exposure: Not asbestos. The treatments reviewed were targeted drugs, given alone or with chemotherapy:
• tyrosine kinase inhibitors: imatinib, dasatinib, sorafenib, sunitinib, gefitinib, erlotinib, vatalanib, cediranib and semaxanib
• bevacizumab and thalidomide
• temsirolimus
• the anti-mesothelin antibody MORab-009
• ranpirnase
• NGR-hTNF
• histone deacetylase inhibitors
• Main results:
  • Across the trials reviewed, response rates to targeted agents ranged from 0–14% as first-line treatment and 0–16% as second-line treatment.
  • Four phase II trials of imatinib alone had no responders. The text says these trials included 94 patients in total. The review's Table 1 lists 17, 11, 25 and 29 patients for the four trials, which add to 82.
  • In a second-line sunitinib trial in malignant pleural mesothelioma, the response rate was 10% and median overall survival was 6.7 months among 53 enrolled patients. Stable disease was seen in 33 patients, which the review reports as 66%. That percentage does not match 33 of the 53 enrolled, and the review does not state its denominator.
  • Zalcman et al. ran a phase II/III trial in inoperable malignant pleural mesothelioma patients; Table 2 lists 111 patients. In a preliminary analysis, disease control at 6 months was 25/34 (73.5%) in the pemetrexed-cisplatin-bevacizumab arm versus 16/37 (43.2%) without bevacizumab (P = 0.010). The response rate in the bevacizumab arm was 14.4%.
  • A randomized phase II trial of 115 chemotherapy-naive patients added bevacizumab to cisplatin and gemcitabine. It showed no improved clinical benefit:
• response rates were 25% with bevacizumab and 22% without
• median overall survival was 15.6 and 14.7 months
  • In first-line use, none of the tyrosine kinase inhibitors dasatinib, vatalanib, gefitinib or erlotinib gave a response rate above 12% or progression-free survival above 4.1 months.
• The authors' conclusion: The authors concluded that:
• disease stabilization was reported in some patients with several targeted treatments
• these drugs might benefit subgroups of patients or work in combination with classic chemotherapy
• none could currently be recommended as standard treatment
• adding bevacizumab to standard treatment merited further evaluation
• Limitations the authors state:
  • The tyrosine kinase inhibitor trials were all phase II trials with limited numbers of patients, so the activity of these drugs is not firmly established.
  • Some of the trials reviewed had somewhat suboptimal designs.
  • Objective response is hard to compare between trials because response evaluation is difficult in malignant pleural mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Clinical Trial, Mesothelioma, Serosal Surface, Prognosis, Tyrosine Kinase Inhibitor, Sunitinib (Sutent), Bevacizumab, Pemetrexed (Alimta).

Related studies

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• Targeted therapies in malignant pleural mesothelioma: a review of clinical studies — L. Greillier, S. Marco, et al. (2011)
• Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements — D.C. Christoph, W.E. Eberhardt (2014)
• Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials — J.M. Mankor, M.J. Disselhorst, et al. (2020)
• Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy? — D. Signorelli, M. Macerelli, et al. (2016)
• Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052) — M.E. O'Brien, R.M. Gaafar, et al. (2013)

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