Based on results from the CheckMate743 trial, the dual regimen of ipilimumab and nivolumab is the standard of care for the treatment of unresectable pleural mesothelioma.1 However, research published last month in the Journal of Thoracic Oncology (JTO) showed that a group of Australian patients treated with the immunotherapy combination experienced higher levels of toxicity than were reported in the clinical trial results. The study is available here.
In Australia, which has one of the highest rates of asbestos-associated diseases in the world, mesothelioma remains an area of unmet need with a 5-year overall survival (OS) rate of 10%.2 First-line immunotherapy with ipilimumab and nivolumab is now a standard of care for resectable pleural mesothelioma following the CheckMate743 (CM743) trial, with supportive data from the later-line single-arm MAPS2 trial.3 The JTO study, Real-World Toxicity and Survival of Combination Immunotherapy in Pleural Mesothelioma—RIOMeso, examines the survival and toxicity of this regimen in real-world practice.2
Author Ned McNamee, BMed, MMed, of Kinghorn Cancer Centre and St. Vincent’s Hospital, Darlinghurst, Australia, and fellow researchers retrospectively collected demographic and clinicopathological data from 119 Australian patients across 11 medical centers who underwent treatment with ipilimumab and nivolumab in both first-line and subsequent settings for pleural mesothelioma. Survival outcomes were assessed using the Kaplan-Meier method, and toxicity was evaluated through the CTCAE v5.0.
The median age of patients was 72, 83% were male, 92% were ECOG ≤1, 50% had previous or current tobacco use history, and 78% had known asbestos exposure. Among the patients, 50% were epithelioid, 19% sarcomatoid, 14% biphasic, and 17% unknown. Ipilimumab and nivolumab were used in first-line therapy in 75% of patients.
- Median overall survival (mOS) for the cohort was 14.5 months.
- Patients treated in the second or later-line had a mOS of 15.4 months.
- No statistically significant difference in mOS was found between epithelioid and non-epithelioid histology.
- Approximately 24% of patients experienced CTCAE grade ≥ 3 adverse events, with colitis being the most frequent.
The RIOMeso study marks a significant milestone as the first detailed report of real-world survival and toxicity outcomes in Australian patients undergoing ipilimumab and nivolumab treatment for pleural mesothelioma, Dr. McNamee said.
The findings suggest that, in real-world practice, combination immunotherapy may have poorer survival outcomes and be more toxic compared with clinical trial data, emphasizing the importance of understanding the treatment landscape beyond controlled trial settings.
However, Dr. McNamee urged caution in interpreting these results.
“There is certainly survival benefit of the Checkmate743 regimen over chemotherapy, especially in the non-epithelioid group; however, perhaps there is more equipoise in epithelioid patients,” he said. “Careful patient selection may mitigate some of the risk of toxicity, but our study demonstrates that the non-chemotherapy option is not necessarily less toxic.”
References
- 1. Peters S, Scherpereel A, Cornelissen R, et al. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022;33(5):488-499. doi:10.1016/j.annonc.2022.01.074
- 2. McNamee N, Harvey C, Gray L, et al. Brief Report: Real-world toxicity and survival of combination immunotherapy in pleural mesothelioma – RIOMeso. J Thorac Oncol. Published online November 15, 2023. doi:10.1016/j.jtho.2023.11.014
- 3. Scherpereel A, Mazieres J, Greillier L, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial [published correction appears in Lancet Oncol. 2019 Mar;20(3):e132]. Lancet Oncol. 2019;20(2):239-253. doi:10.1016/S1470-2045(18)30765-4
