In the phase III CONFIRM trial reported in The Lancet Oncology, Dean A. Fennell, FRCP, PhD, and colleagues found that nivolumab improved progression-free and overall survival vs placebo in patients with relapsed malignant mesothelioma.
In October 2020, the combination of nivolumab and ipilimumab was approved for the first-line treatment of unresectable malignant pleural mesothelioma.
![Dean A. Fennell, FRCP, PhD](/media/14016223/1-fennell.jpg)
Dean A. Fennell, FRCP, PhD
As stated by the investigators, “No phase III trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma [that has] progressed following platinum-based chemotherapy.”
Study Details
In the double-blind multicenter trial, 332 patients with pleural or peritoneal mesothelioma who had received first-line platinum-based chemotherapy and had radiologic evidence of disease progression were randomly assigned 2:1 between May 2017 and March 2020. Patients received either nivolumab at 240 mg (n = 221) or placebo (n = 111) every 2 weeks until disease progression, unacceptable toxicity, or for a maximum of 12 months.
Overall, 95% of patients in each group had pleural mesothelioma; 88% in each group had epithelioid histology. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, with analysis adjusted for epithelioid type.
Progression-Free and Overall Survival
Median follow-up was 11.6 months (interquartile range [IQR] = 7.2–16.8 months). Median progression-free survival was 3.0 months (95% CI = 2.8–4.1 months) in the nivolumab group vs 1.8 months (95% CI = 1.4–2.6 months) in the placebo group (adjusted hazard ratio [HR] = 0.67, 95% CI = 0.53–0.85, P = .0012). Rates at 1 year were 14.2% (95% CI = 9.9%–19.3%) vs 7.2% (95% CI = 3.1%–13.8%).
Subsequent systemic treatment was received by 35% of patients in the nivolumab group and 35% of the placebo group, with 11% of the placebo group receiving nivolumab.
Median overall survival was 10.2 months (95% CI = 8.5–12.1 months) in the nivolumab group vs 6.9 months (95% CI = 5.0–8.0 months) in the placebo group (adjusted HR = 0.69, 95% CI = 0.52–0.91, P = .0090). Overall survival at 1 year was 43.4% (95% CI = 36.3%–50.4%) vs 30.1% (95% CI = 21.0%–39.6%).
Among 252 patients with quantifiable PD-L1 expression, there was no evidence of an association of PD-L1 status with progression-free survival (HR for interaction = 1.55, P = .16) or overall survival (HR for interaction = 1.16, P = .70).
Objective responses (all partial) were observed in 25 patients (11%) in the nivolumab group vs 1 (1%) in the placebo group (odds ratio = 14.0, P = .00086). Among responders in the nivolumab group, median time to response was 84 days (95% CI = 81–145 days) and median duration of response was 143 days (95% CI = 92–211 days).
KEY POINTS
- Nivolumab improved progression-free and overall survival vs placebo.
- Median progression-free survival was 3.0 vs 1.8 months; median overall survival was 10.2 vs 6.9 months.
Adverse Events
Treatment-related adverse events of any grade occurred in 74% of patient in the nivolumab group vs 56% of the placebo group. The most common grade ≥ 3 treatment-related adverse events in the nivolumab group were diarrhea (3% vs 2% in the placebo group) and infusion-related reaction (3% vs 0%).
Serious adverse events occurred in 41% vs 44% of patients, most commonly dyspnea (8% vs 9%) and pneumonia (6% vs 5%). Adverse events led to treatment discontinuation in 14% vs 3%, most commonly due to infusion-related reaction (1.8%) and diarrhea (1.3%) in the nivolumab group. No treatment-related deaths occurred in either group.
The investigators concluded, “Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have [had disease progression] on first-line therapy.”
Dr. Fennell, of the Mesothelioma Research Programme, Leicester Cancer Research Centre, University of Leicester, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Stand up to Cancer–Cancer Research UK and Bristol Myers Squibb. For full disclosures of the study authors, visit thelancet.com.