Invited discussant of the CheckMate 743 trial, Dean A. Fennell, FRCP, PhD, Director of the Mesothelioma Research Program and Chair of Thoracic Oncology at The University of Leicester and University Hospitals of Leicester, United Kingdom, noted the combination of nivolumab and ipilimumab has been previously tested in mesothelioma in the INITIATE and MAPS2 trials, but they were in the relapsed setting.1,2
“Use of nivolumab and ipilimumab in the front-line setting in CheckMate 743 led to significantly higher overall response rates compared with previous trials of immunotherapy, perhaps related to the chemonaive state compared with INITIATE and MAPS2,” said Dr. Fennell. “Progression-free survival was also longer than what was previously reported, but it should be noted that this immunotherapy combination still has significant activity in the relapsed setting.”
Dean A. Fennell, FRCP, PhD
Focus on Nonepithelioid Disease
Dr. FennelL also highlighted pivotal data from Checkmate 743 showing a “transformative improvement” in patients with nonepithelioid mesothelioma who received immunotherapy. Analysis by histology showed a distinct difference between treatment arms, said Dr. Fennell, who noted a doubling of overall survival in patients with nonepithelioid mesothelioma who were randomly assigned to nivolumab plus ipilimumab compared with chemotherapy (18.1 months vs 8.8 months). This effect was related to the poor performance of chemotherapy in this subgroup, ie, a negative prognostic effect of nonepithelioid histology, which exhibited marked drug resistance compared to the epithelioid subgroup, possibly due to epithelial-mesenchymal transition. In contrast, immunotherapy and chemotherapy were statistically equivalent in the epithelioid subgroup.
“In the nonepithelioid subgroup, the [ipilimumab/nivolumab] survival curve exhibited a degree of durability with immunotherapy that is way beyond what has been seen previously with chemotherapy,” said Dr. Fennell. “These results herald a new standard of care in this setting.”
“Looking forward, the combination of chemotherapy and immunotherapy or selective targeting of nonepithelioid mesothelioma could further extend benefit for patients with nivolumab plus ipilimumab,” Dr. Fennell concluded.
DISCLOSURE: Dr. Fennell reported financial relationships with AstraZeneca, Astex Therapeutics, Bayer, BMS, Atara Biotherapeutics, Boehringer Ingelheim, Clovis Oncology, Eli Lilly, Lab 21, MSD, Inventiva, and Roche.
REFERENCES
1. Calabrò L, Morra A, Fonsatti E, et al: Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: An open-label, single-arm, phase 2 study. Lancet Respir Med 3:301-309, 2015.
2. Calabrò L, Morra A, Giannarelli D, et al: Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): An open-label, non-randomised, phase 2 study. Lancet Respir Med 6:451-460, 2018.
