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Fitzgerald et al. J Cancer Metastasis Treat 2021;7:54 https://dx.doi.org/10.20517/2394-4722.2021.97 Page 9 of 11

Figure 2. A proposed framework for the evidence-based treatment of unresectable malignant pleural mesothelioma.

not been borne out in the phase III setting.

Options for the treatment of unresectable MPM in both the front-line and subsequent-line settings remain
limited. However, the additions of robust data in immunotherapy and supplemental anti-VEGF treatments
to traditional chemotherapy have unquestionably changed the standard of care. Clinicians are now able to
choose between standard chemotherapy, chemotherapy plus bevacizumab, or nivolumab plus ipilimumab
as first line treatments for unresectable malignant pleural mesothelioma [Figure 2].

Future trials will build on immunotherapy backbones. Despite representing a significant advance, the
objective response rate of 40% with dual checkpoint blockade seen in Checkmate 743 leaves the majority of
patients without response to treatment . Efforts to increase efficacy by adding additional agents are highly
[10]
anticipated. The phase II data for chemo-immunotherapy combinations has been exceptional, and is already
infiltrating clinical practice in selected circumstances, although notably phase II data have often not
[28]
translated to positive phase III trials in MPM, as seen with Nintedanib and other anti-VEGF agents . As
immunotherapy solidifies its place within front-line treatment, second-line trials examining the response
rates to chemotherapy with or without bevacizumab after front line ipilimumab plus nivolumab will be
needed to determine optimal sequencing of treatments, and combinations with other novel agents will
hopefully further improve outcomes.