New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials

Our plain-English summary of New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials, by S. Kotova, R.M. Wong, R.B. Cameron (Cancer Management and Research, 2015).

The study

• Authors: S. Kotova, R.M. Wong, R.B. Cameron
• Journal: Cancer Management and Research
• Published: 2015;7:51-63
• Type of article: Review
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease.

In plain English

This article was a review, not a new study. The authors summarized published and ongoing clinical trials and laboratory work on treatments for malignant pleural mesothelioma, which the article describes as an asbestos-induced cancer. They noted 192 registered trials and wrote that more than 1,000 patients had taken part in the trials the review covered over the last decade. In an earlier trial the authors cite, pemetrexed plus cisplatin gave a median survival of 12.1 months, compared with 9.3 months for patients given cisplatin alone. Trials of drugs that block the EGFR and VEGF growth signals did not show improved survival. In a cited trial of tremelimumab, an immune checkpoint drug, objective responses occurred in two of 29 patients. Other early reports described partial responses to a mesothelin-targeted immunotoxin and a dendritic cell vaccine, immune activation after gene therapy, and survival figures after gene therapy, photodynamic therapy and cryotherapy. For povidone-iodine (betadine) lavage, the authors wrote that convincing evidence of efficacy was still lacking. The authors concluded that patients should be placed in randomized prospective clinical trials to determine the best therapy.

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 preclinical and early clinical studies and ongoing trials of treatments for malignant pleural mesothelioma
• Who was studied: Published and registered trials of treatments for malignant pleural mesothelioma. The authors cite 192 registered trials on Clinicaltrials.gov and more than 1,000 patients in the trials covered over the last decade. Some animal and laboratory studies were also reviewed.
• Exposure: The review did not study asbestos exposure. It covered treatments: chemotherapy, surgery, radiation, tyrosine kinase inhibitors (EGFR and VEGF blockers), mesothelin-targeted antibodies, toxins and vaccine, IL-4 receptor toxins, immune checkpoint inhibitors, gene therapy, dendritic cell vaccines, photodynamic therapy, heated chemotherapy, povidone-iodine lavage and cryotherapy. Asbestos is mentioned only as the cause of the disease.
• Main results:
  • In a cited phase III trial of 456 patients, median survival was 12.1 months for those given pemetrexed and cisplatin versus 9.3 months for those given cisplatin alone.
  • Clinical trials of EGFR-blocking drugs (gefitinib, erlotinib) did not show improved survival.
  • The only randomized trial of standard chemotherapy with or without the VEGF antibody bevacizumab showed no difference in disease progression or overall survival.
  • In a cited phase I trial of the antimesothelin antibody MORAb-009, eleven of 24 patients had stable disease.
  • In a cited study of the SS1P immunotoxin combined with immune suppression, three of ten patients had a partial response.
  • In a cited phase II trial of tremelimumab in 29 patients with chemotherapy-resistant advanced mesothelioma (28 pleural, 1 peritoneal), objective responses occurred in two of 29 patients and disease stabilization in nine (31%). Overall survival was 48% at 1 year and 37% at 2 years.
  • In a cited trial of intrapleural adenovirus herpes simplex thymidine kinase/ganciclovir suicide gene therapy in 34 patients, median survival was as high as 15 months at the highest viral doses. Some patients had prolonged survival, which the review says suggested induction of antitumor immunity.
  • In cited trials of adenoviral interferon gene therapy, the review reported immune effects such as activation of natural killer cells. Survival ranged from 1 to 22 months, and neutralizing antibodies limited repeated treatments.
  • In a cited pilot phase I study of a dendritic cell vaccine, there were three partial responses and an overall median survival of 19 months.
  • In a cited phase I–II experience with photodynamic therapy after pleurectomy/decortication, median disease-free progression was 15 months and overall survival was over 40 months.
  • For hyperthermic povidone-iodine (betadine) lavage after surgery, the treatment was well tolerated, but the authors wrote that convincing evidence of efficacy was still lacking.
  • In a cited report of percutaneous cryoablation in 24 patients with limited local recurrence after pleurectomy/decortication, median survival was 11.4 months after first therapy (36.1 months after surgery).
• The authors' conclusion: The authors concluded that survival remains poor despite some benefit from surgery and combination chemotherapy. They wrote that patients should be placed in randomized prospective clinical trials to determine optimal therapy.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Clinical Trial, Chemotherapy, Mesothelin, checkpoint inhibitors.

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