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Treating mesothelioma in
2021: what is the role of
surgery and immunotherapy?

Dr Anna Bibby
Consultant Respiratory Physician – North Bristol NHS Trust
Honorary Senior research Associate – University of Bristol
Disclosures
• None
Mesothelioma
• Mesothelial malignancy
• Caused by previous asbestos exposure
• Rising incidence worldwide
• Poor prognosis
– Median survival ~12 months
• Historically limited treatment options
– Pemetrexed + cis/carboplatin1 2
• Recent evidence for bevacizumab + chemo3

1. Vogelzang et al, 2003 2. Ceresoli et al, 2008 3. Zalcman et al 2016

Surgery
Surgery

• Should “radical surgery” (including extrapleural pneumonectomy or

pleurectomy/decortication) be used in patients with MPM?

• Should partial pleurectomy, compared to talc pleurodesis, be used as a

palliative procedure in patients with symptomatic MPM?
Surgery in mesothelioma
• Extra-pleural pneumonectomy (EPP)

• Extended pleurectomy/decortication (EP/D)

• Partial pleurectomy (PP)

Rice 2012
Radical surgery - EPP
• Multiple surgical series & registry data report longer survival post-EPP
• MARS trial
• Feasibility RCT: EPP (n=24) vs no EPP (n=26)
• Primary outcome: Full scale RCT not feasible
– Only 16/24 completed EPP
– 3/26 in no EPP group underwent EPP out of trial
• High mortality overall :
– 4/19 patients who underwent EPP died peri-operatively
• Lower quality of life in EPP group (non-significant)

Treasure et al, 2011

EPP

Treasure et al, 2011

EP/D
• Lower peri-operative mortality vs EPP
– RR 1.7 (95% CI 0.9-2.8) vs 4.5 (3.2-6.0), p<0.051
– HR 0.53 (0.31-0.91)2
• Fewer perioperative complications
– 27.9% vs 62.0%, p<0.00012
– HR 0.44 (0.30-.63)2
• Similar long-term survival
– 27% (14.7-41.9) vs 24% (16.1-33.1) at 2 years, p=0.21

• MARS2 in follow up, results expected next year3

1. Taoili et al, 2015 2. Cao et al, 2014 3. Lim et al, 2016
Palliative partial pleurectomy
• Meso-VATS RCT1
• PP (n=87) vs talc pleurodesis (n=88)
• Primary outcome was 1 year survival
– 52% (41–62) vs 57% (46–66)
– HR 1·04 (95% CI 0·76–1·42), p=0·81
• Overall survival also similar
– 13·1 months (IQR 7·3–20·3) vs 13·5 months (7·3–21·1)
• VATS-PP more expensive
– ~ €4500 per case, ~ €140,000 per QALY

1. Rintoul et al, 2014

PP and non-expandable lung
• NEL common in MPM (33% of people with effusions)1
• Associated with shorter survival 1
• What is role of PP to release trapped lung?

• Meso-TRAP (NCT03412357)
• Randomised feasibility study of VATS-PP vs IPC in NEL
• Challenging trial to undertake:
– only 10% of screened participant eligible
– 9 people randomised

1. Bibby et al, 2019

ERS guidance
• Surgery may be appropriate for highly selected MPM patients
• EP/D rather than EPP, performed in centres of excellence
• As part of multimodality treatment
• Not in patients with:
– Sarcomatoid histology
– N2 disease or
– stage IV
other than in research trials

Scherpereel et al, 2020

Immunotherapy
Immune checkpoint inhibition
Tumour antigen

T cell receptor
Tumour cell
α

-
-
T cell - PDL-1
- - PDL-1
PDL1 inhibitor
PD1 inhibitor
PD1CTLA4
receptor
Immunotherapy
• Several disappointments

Maio et al, 2017 Popat et al, 2020

Checkmate 743
• Nivo/Ipi (n=303) vs pem/cis (n=302)

Baas et al, Lancet, 2021

Checkmate 743

Baas et al, Lancet, 2021

Checkmate 743
• Greater survival benefit with nivo/ipi if PDL1>1%
– HR for mortality 0·69 (95% CI 0·55–0·87) vs 0·94 (0·62–1·40)

• More grade 3 or 4 AE with ICI

– Mostly diarrhoea & pruritis vs nausea & neutropaenia with chemo
– But when adjusted for treatment duration, AE incidence similar

• Three (1%) treatment related deaths with ICI

– pneumonitis, encephalitis, heart failure
– Vs one (<1%) in chemotherapy group (myelosuppression)
Baas et al, Lancet, 2021
CONFIRM

Fennel et al, WCLC 2020

Other immunotherapeutic approaches
• Oncolytic viruses
• Vaccine therapy
• Autologous dendritic cells
• CAR T cells

• All undergoing early phase clinical trials, with some signs of promise
Immunotherapy summary
• Nivo/ipi approved for front-line use in MPM
– Of particular benefit in non-epithelioid histology cf chemo
– NB potential toxicity
• Second-line nivolumab received interim approval in UK
Thank you