Aggressive surgery for the treatment of malignant pleural mesothelioma (MPM) — unless part of a clinical trial — is no longer being recommended in the United Kingdom.
The British Thoracic Society recently published its Mesothelioma Management Guidelines for 2018 and removed surgery from its recommendations. The belief was that potential harm was not worth the risk.
The backtrack on surgery included the extrapleural pneumonectomy (EPP), the extended pleurectomy and decortication (P/D) and the partial pleurectomy (PP) — all of which are being done at cancer centers in the United States.
“Surgery is a controversial area. There is a difference of opinion, from our practice in the U.K. and much of Europe, than the practice in the [United] States,” Dr. Anna Bibby, University of Bristol Medical School and North Bristol NHS Trust, told Asbestos.com. “American guidelines are more encouraging of surgery. It comes down to how evidence is interpreted, assessing harm and benefits.”
Study Looks at the Future of Treatment
Bibby is the lead author of a recently published study in the Clinical Respiratory Journal that reviewed hundreds of clinical trials and studies over the past three decades.
It includes current ones.
The study provided a look at potential future treatment options. Some of the trials also were used by the British Thoracic Society in making its latest recommendations.
Of the 258 studies, 35 were selected for inclusion in the review.
Among those used:
The Mesothelioma and Radical Surgery (MARS) feasibility study examining the EPP surgery.
The Meso-VATS trial that observed the mostly palliative PP surgery.
“Current evidence does not support surgical intervention. However, investigations are ongoing, including the MARS2 trial that is looking at the less-aggressive (E)P/D surgery,” Bibby wrote in the study.
The Thoracic Society Guidelines include these recommendations:
Do not offer VATS-PP over talc pleurodesis in MPM.
Do not offer EPP in MPM.
Do not offer EPD outside of a clinical trial.
The guidelines also recommend radiotherapy only with palliative intent and not to prevent future tumor development, in contrast to specialty centers within the U.S.
Immunotherapy May Be the Answer
Bibby’s study called bevacizumab the most significant development in mesothelioma treatment in the last decade.
Bevacizumab, which is used in combination with chemotherapy, slows or stops the growth of cancer cells by inhibiting the formation of new blood vessels in tumors. It is also known as an anti-angiogenesis agent.
Nintedinib is a drug that works in a similar fashion and has been used successfully with mesothelioma.
The study praised trials being done with drugs that target the cell-surface protein mesothelin, which is overexpressed in the most common type of mesothelioma.
Mesothelin also has become a target of the burgeoning gene therapy exploration in a variety of cancers, including mesothelioma.
There are several ongoing trials that involve finding reliable biomarkers that can determine which patients are most likely to benefit from this type of therapy.
Immunotherapy, which allows a patient’s own immune system to kill cancer cells, also is being closely watched in several clinical trials involving drugs such as Opdivo (nivolumab), ipilimumab, tremelimumab and Imfinzi (durvalumab).
“The future [for treatment] looks brighter than it has been for several decades. We will soon have more options than we currently do,” she said. “And that will be great. The field of mesothelioma research has expanded massively.”
Focus Is on Emerging Therapies in UK
Many of these promising therapies, though, are still only available now through clinical trials, or special access.
In the U.S. the only FDA approved treatment for mesothelioma involves chemotherapy, radiation and surgery.
“Immunotherapy is a very promising area, and it’s looking more and more like combinations of immunotherapy are more effective than single agents,” she said. “We’re moving more toward targeted, personalized treatment, and that’s a good thing.”
She emphasized the importance of clinical trials in advancing the treatment of a rare and aggressive cancer such as mesothelioma, which has no definitive cure.
“Patient involvement is hugely important,” she said. “There may be cultural differences here, but in the U.K., we find patients to be very engaged in research and keen to participate in trials. They recognize how important it is, along with opportunity to get treatment that might not be otherwise available.”