Nivolumab significantly prolongs survival outcomes, when compared with placebo, in patients with relapsed malignant mesothelioma, according to results of the CONFIRM trial.
“To our knowledge, the CONFIRM trial is the first randomized, phase 3 study to show improved overall survival in patients with relapsed malignant pleural and peritoneal mesothelioma,” the researchers wrote in The Lancet Oncology.
The trial (ClinicalTrials.gov Identifier: NCT03063450) enrolled 332 patients with relapsed disease — 316 with pleural and 16 with peritoneal mesothelioma. There were 293 patients with epithelioid histology, 230 with prior asbestos exposure, and 252 with quantifiable PD-L1 expression. The patients’ median age was 70 years.
Patients were randomly assigned to receive nivolumab (221 patients) or placebo (111 patients) until disease progression or for a maximum of 12 months.
The median follow-up was 11.6 months. The overall response rate (all partial responses) was significantly higher in the nivolumab arm than in the placebo arm — 11% and 1%, respectively (odds ratio 14.0; 95% CI, 2.4 to not estimable, P =.00086).
In the nivolumab arm, the median time to response was 84 days, and the median duration of response was 143 days. For the single responder in the placebo arm, the time to response was 132 days, and the duration of response was 212 days.
The median progression-free survival (PFS) was 3.0 months in the nivolumab arm and 1.8 months in the placebo arm (adjusted hazard ratio [aHR], 0.67; 95% CI 0.53-0.85; P=.0012). The 1-year PFS rate was 14.2% and 7.2%, respectively.
The median overall survival (OS) was 10.2 months in the nivolumab arm and 6.9 months in the placebo arm (aHR, 0.69; 95% CI, 0.52-0.91; P =.0090). The 1-year OS rate was 43.4% and 30.1%, respectively.
There was no evidence to support PD-L1 expression (≥1%) as a predictor of OS (HR, 1.16; 95% CI, 0.56-2.40; P =.70) or PFS (HR, 1.55; 0.85-2.83; P =.16).
Treatment-related adverse events (TRAEs) were seen in 74% of patients in the nivolumab arm and 56% of those in the placebo arm. Serious TRAEs were observed in 13% and 7%, respectively.
The most common grade 3 or higher TRAEs (in the nivolumab and placebo arms, respectively) were diarrhea (3% and 2%) and infusion-related reactions (3% and 0%). There were no treatment-related deaths in either arm.
Disclosure: This research was partially supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Fennell DA, Ewings S, Ottensmeier C, et al. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): A multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol. Published online October 14, 2021. doi:10.1016/S1470-2045(21)00471-X