Immune checkpoint inhibition for the treatment of mesothelioma

Combination chemotherapy is currently standard care for advanced mesothelioma

Anna K Nowak

2019

Scholarcy highlights

  • Combination chemotherapy is currently standard care for advanced mesothelioma
  • A diagnosis is preferably made on histology from tumor biopsy, taken thoracoscopically or percutaneously, but can be made on pleural effusion cytology in epithelioid subtype tumors
  • The median progression-free survival was 6.2 months and median overall survival not reached at publication. It appears that the addition of either ipilimumab or tremelimumab to progressive disease pathway blockade adds a modest increment to the objective tumor response rate, with the only randomised study demonstrating a signal for a longer progression free survival and overall survival with the combination
  • The Australian single arm phase II DREAM clinical trial started in late 2016 and rapidly recruited 54 patients to a combination of cisplatin and pemetrexed with the anti PD-L1 antibody durvalumab given on the same day, three weekly, for a maximum of six cycles of combined treatment
  • In the context of immune checkpoint blockade, single agent studies investigating second line anti-PD1 therapy in patients with mesothelioma have shown that expression of PD-L1 in pre-treatment biopsies did not correlate with patient outcome
  • DETERMINE recruited 571 patients, and was a negative study, with a hazard ratio of 0.92 for overall survival, and a median OS of 7.7 months vs. 7.3 months
  • It would be appropriate to give a numerical score, to examine both tumour and immune infiltrate but be able to report separately, and to report on a range of cut-points including >1%, >5%, and >50%. While these initial studies suggest that pre-treatment PD-L1 expression in mesothelioma tumors may not be a useful indicator of those patients most likely to succeed on single agent anti-PD-1 treatment regimens, harmonisation of methods for PD-L1 testing in mesothelioma is required before it can be ruled out as a predictive biomarker
  • Incorporating well-designed biomarker testing into current and future clinical trials is critical for our future interpretation and understanding of appropriate patient selection for checkpoint inhibition, and the design and use of rational combination therapies

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