Treatment & Clinical Trial Information
Treatment
Immunotherapy
Ipilimumab and Nivolumab
This dual immunotherapy treatment was approved in July 2022 as a first line treatment for all mesothelioma sites and subtypes. This was after results of the checkmate 743, phase 3 trial were published showing increased overall survival of 18.1 months versus 14.1 months with standard chemotherapy.
The drugs work by blocking proteins that stop the immune system from identifying and attacking cancer cells and help the immune system to identify these. The drugs are given intravenously every 3 weeks in 6 weekly cycles. Both drugs are given on day 1 of the cycle and on day 21 nivolumab is given alone. This continues for up to 2 years as long at the treatment is working, by either reducing the volume of cancer or stopping further growth.
Treatment may be deferred or stopped during the 2 years if patients experience adverse side effects depending on their severity.It is up to the treating oncologist to decide if treatment can be continued with both drugs, nivolumab alone or if treatment should be stopped completely. Scans are done 3 monthly to monitor the cancer. Some autoimmune conditions may mean a patient cannot be safely treated with immunotherapy and they may be offered chemotherapy.
Immunotherapy
Nivolumab as a second/subsequent treatment
If a patient has received chemotherapy as a first line treatment prior to approval of ipilimumab and nivolumab in July 2022 they can access single agent nivolumab as a second line treatment. The phase 3 trial (confirm) showed improved overall survival in patients with relapsed malignant pleural and peritoneal mesothelioma versus placebo. It was used during covid as a second or subsequent line treatment rather than chemotherapy as it was felt to be safer and less immunocompromising, limiting hospital admissions.In this situation treatment is given 4 weekly until disease progression.
Nivolumab as a monotherapy is approved as a 2nd ( and subsequent) line treatment in Scotland. There is currently no provision for this in England, Wales or Northern Ireland.
Chemotherapy
Pemetrexed and platinum
This is a combined chemotherapy treatment now used as a second line treatment in mesothelioma in all sites of disease and subtypes.It can be used first line in patients that have autoimmune conditions that prevent them having immunotherapy treatment. Chemotherapy was the foundation in the treatment of mesothelioma since 2004 when the EMPHACIS trial showed improvement in response rate, time to progression and overall survival for this combined treatment compared with cisplatin alone. Dependent on the treatment centre and oncologists patients will be offered a combination of pemetrexed and carboplatin or cisplatin.
It is given intravenously every 3 weeks for 4-6 cycles.At the end of treatment, a CT scan is performed to assess if the treatment has been successful. If it has the patient will then enter a surveillance stage where CT scans are performed at regular intervals (usually 3 monthly). If treatment works for 6 months or more the patient may be able to undergo a rechallenge.
Chemotherapy
Vinorelbine
The use of systemic anti-cancer therapy in mesothelioma beyond Pemetrexed and Platinum (and more recently, Ipilimumab and Nivolumab) varies across the UK with some Oncologists supportive of the use of Vinorelbine and others less enthusiastic. The Phase II VIM trial showed modest but statistically significant progression free survival in patients with relapsed malignant mesothelioma, with an acceptable safety profile compared with active symptom control. There is therefore evidence to consider the use of low dose, weekly administration of Vinorelbine in the third line setting or earlier if other standard treatments are contraindicated.
Radiotherapy
The use of radiotherapy in mesothelioma has largely focused on symptom control. In the UK, clinical trials have looked at different doses and schedules of treatment to improve pain control. Preliminary findings from the Phase II SYSTEMS-2 study, which compared a higher dose of radiotherapy to the standard dose, found a significant increase in life expectancy. This was a somewhat surprising finding. The main aim of the study was to see if the escalated dose provided better pain control. The higher dose of radiotherapy was associated with a small increase in the number of patients experiencing improved pain control but the difference was not statistically significant.
Other trials examined the use of Prophylactic Irradiation of Tracts (PIT) to prevent port site seeding and the development of painful lumps and nodules (PIT and SMART). Both studies concluded that there was no role for the routine use of PIT following tests or treatment for mesothelioma of the lung. Instead, radiotherapy is used to treat painful areas and nodules as they develop.
Surgery
The use of radical thoracic surgery in mesothelioma has been hotly debated for many years. The first MARS study involved the use of Extra Pleural Pneumonectomy (EPP) with standard chemotherapy available at the time versus chemotherapy alone. The outcomes of this feasibility study led to a number of thoracic centres across the UK reconsidering the role of radical surgery in mesothelioma. The second MARS study (MARS2) involved the use of Extended Pleurectomy Decortication (EPD) plus chemotherapy (pemetrexed and Carboplatin) versus chemotherapy alone. The study reported that extended pleurectomy decortication was associated with worse survival and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone.
The design of the study has been carefully examined since the results were shared and published and a number of factors have been highlighted that could account for the poor survival and serious adverse events. These include accepting all cell types into the surgical arm, not performing PET CT as routine and fewer numbers of surgical patients completing the full course of chemotherapy due to post operative complications and recovery.
The debate about the role of radical surgery therefore continues. Many thoracic centres across the UK will no longer offer EPD however there are some centres who will consider the option in a carefully selected group of patients.
Access to non-NHS funded therapies
Outside of the NHS setting a number of systemic treatment options are available when seeking a private oncology opinion. The MAPS study was conducted in the first line setting before NHS access to Ipilimumab and Nivolumab for unresectable PS 0-1 patients. This concluded that the addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma. For some people with private medical insurance or the means to fund treatment privately, the addition of Bevacizumab to standard chemotherapy treatment could be an alternative first line option. However, for many patients who go on to access treatment privately, they do so via funding from successful asbestos litigation cases. As most legal cases take a number of months or longer to settle, this treatment is mostly accessed privately as a second or subsequent line option on progression of disease following standard first line therapy.
Another consideration beyond standard NHS systemic treatment options is the use of Ramucirumab and Gemcitabine. The RAMES study concluded that Ramucirumab plus gemcitabine significantly improved overall survival after first-line standard chemotherapy, with a favourable safety profile.
Clinical Trials
Mesothelioma UK is the only national UK charity dedicated to mesothelioma. One of its aims is to ensure people affected by mesothelioma have access to treatment and clinical trials that may improve quality of life and extend life expectancy.
Mesothelioma UK recognises that not all patients have equitable access to clinical trials so by providing information about current clinical trials available on its website, in newsletters and via the clinical trial app, it aims to raise awareness.
Clinical trials currently available:
First line:
HIT-MESO – Hemithoracic irradiation with proton therapy in malignant pleural mesothelioma.
Patients are randomized to receive proton therapy vs disease surveillance. Proton therapy will be delivered at either UCLH or The Christie in Manchester.
Sites currently recruiting:
Cambridge, Kings Lynn, Manchester (recruitment and treatment site), Reading, London UCLH (recruitment and treatment site), Clatterbridge, London Barts, Chelmsford, Betsi Cadwalader, Essex, Cardiff, Maidstone, Portsmouth, Torbay, Leicester, Freeman Hospital – Newcastle, Western Park -Sheffield, Castle Hill – Hull.
Observational studies:
ASSESS-MESO – A prospective observational cohort study collecting data on demographics, symptoms and biomarkers in people with mesothelioma that will provide a resource for future trials.
Sites currently recruiting:
Leicester, Sherwood, Sheffield, Oxford, Manchester, Gloucester, Clatterbridge, Bristol, Bath, Cardiff, Morecombe, Taunton, Wales, Tyneside, Plymouth, Glasgow, Newcastle.
For more information or to get access to the clinical trials app, please use this link.
The Mesothelioma UK Research Centre at the University of Sheffield
The Research Centre was established in July 2020 to conduct a portfolio of robust and rigorous research. The aim is to gain a reputation for excellence and for the research to benefit the care of people diagnosed with mesothelioma and their families.
For more information of trials currently available, please click here.