FDA Approval Summary: Nivolumab in Combination with Ipilimumab for the Treatment of Unresectable Malignant Pleural Mesothelioma

Abstract

On October 2, 2020, FDA approved nivolumab with ipilimumab as first-line treatment for adult patients with unresectable malignant pleural mesothelioma (MPM). The approval was based on results from Study CA209743 (CHECKMATE-743), an open-label trial of patients with MPM randomized to receive nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302). Overall survival (OS) was improved for patients who received nivolumab and ipilimumab, with a median OS of 18.1 months [95% confidence interval (CI), 16.8–21.5] compared with 14.1 months (95% CI: 12.5–16.2; HR, 0.74; 95% CI, 0.61–0.89; P = 0.002), for patients who received chemotherapy. The magnitude of benefit was larger for patients with non-epithelioid versus epithelioid histology. Additional clinical pharmacology data support an alternative dosing regimen of nivolumab than evaluated in the trial, which will reduce the number of required treatment visits. This application was reviewed under FDA's Project Orbis, in collaboration with Australia's Therapeutic Goods Administration, Switzerland's Swissmedic, Health Canada, and Brazil's National Health Surveillance Agency or ANVISA (Agência Nacional de Vigilância Sanitária). Nivolumab and ipilimumab is the first drug regimen approved by FDA for MPM since 2004.

Fibrosis in Mesothelioma: Potential Role of Lysyl Oxidases

“…Checkpoint inhibitors have been approved by the FDA for the treatment of mesothelioma [ 11 ]. Coupled with lysyl oxidase inhibitors’ anti-fibrotic activity and possible regulation of immune cell infiltration [ 125 , 194 ], their combination has potential as a treatment option for mesothelioma.…”

“…Recently, the addition of Bevacizumab to this regimen was approved for first-line therapy [ 10 ]. The dual checkpoint inhibitor immunotherapy (Ipilimumab/Nivolumab) was FDA-approved for use in treatment of naive mesothelioma patients [ 11 ], based on evidence generated in the CheckMate 743 trial [ 12 ]. Despite showing only similar efficacy to chemotherapy for both median progression-free survival (PFS) and objective response rate (ORR), the dual-immunotherapy regimen demonstrated significantly improved duration of response (DOR).…”

Mesothelioma: A Case in a Diagnostic Timeline and the Efficiency of Robot-Assisted Surgery

“…Other chemotherapy drugs and combinations have been also used [ 6 , 7 ]. There are also other protocols as second- of third-line treatment that include immunotherapy and local treatment [ 8 ]. Several different treatments have been investigated like gene therapy, cryotherapy ablation, photodynamic therapy, virotherapy, and hyperthermia intrathoracic chemotherapy which is experimental [ 5 , 9 , 10 ].…”

Current Management and Future Perspective in Pleural Mesothelioma

“…Since 2020, the combination of nivolumab and ipilimumab has represented the most effective treatment in pleural mesothelioma [ 19 ]. The benefit is even more robust in tumors of the non-epithelioid subtype, which is generally attributed as a disease with high tumor burden, rapid progression, chemotherapy resistant and the worst prognosis, to mention a few.…”