Immune Checkpoint Inhibition for Unresectable Malignant Pleural Mesothelioma

AbstractImmune checkpoint inhibitors (ICI) have shown important but variable efficacy in mesothelioma despite a lack of strong biological rationale. Initial trials assessed ICI monotherapy in patients with relapsed mesothelioma, with objective response rates (ORR) between 4.5 and 29%, median progression-free survival (PFS) between 2.5 –6.2 months, and median overall survival (OS) between 7.7 and 18.0 months. In randomised trials of chemotherapy pre-treated patients, nivolumab was recently shown to improve PFS compared to placebo, but tremelimumab was not superior to placebo, and there was no difference in OS between pembrolizum ab and chemotherapy. However, response to combination ICI appear more promising in both pre-treated and treatment-naïve mesothelioma. The randomised Phase 3 trial of upfront ipilimumab-nivolumab versus platinum-pemetrexed chemotherapy demonstrated improved OS favouring ipilimumab-nivolumab (HR 0.74 , 96.6% CI 0.60–0.91;p = 0.0020), establishing this regimen as a new standard of care, especially in non-epithelioid histological subtypes. However, initially PFS was poorer in the ipilimumab-nivolumab than chemotherapy treatment arms. A single-arm Phase 2 trial of upfront platinum chemotherapy and durvalumab met its primary endpoint, with a 6-month PFS of 57% (95% CI 44 –70) with chemo-immunotherapy under evaluation as an alternative upfront regimen. Several questions remain unanswered. Comparative studies of chemo-immunotherapy versus chemotherapy a...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research