For patients with relapsed malignant mesothelioma, nivolumab (Opdivo) monotherapy is an effective treatment option, according to preliminary results of the phase 3 CONFIRM study, presented at the 2021 International Association for the Study of Lung Cancer meeting.
Nivolumab, a PD-1 inhibitor, has previously demonstrated activity in 2 single-arm phase 2 clinical trials among patients with malignant mesothelioma, said lead investigator Dean Fennell, FRCP, PhD, Chair, Thoracic Medical Oncology, University of Leicester, England, who discussed the results.
The standard first-line therapy for malignant mesothelioma is a chemotherapy doublet comprised of pemetrexed and cisplatin or carboplatin. In October 2020, the FDA approved the combination of nivolumab plus ipilimumab (Yervoy) for unresectable malignant pleural mesothelioma, which accounts for 80% to 90% of malignant mesothelioma cases.
Malignant mesothelioma is intractable, and no phase 3 clinical trial has yet shown overall survival (OS) improvement, Dr Fennell said.
CONFIRM investigators at 24 UK centers enrolled 332 adults with previously treated, unresectable, histologically confirmed malignant mesothelioma (either pleural or peritoneal), and Eastern Cooperative Oncology Group performance status 0-1. The patients were randomized in a 2:1 ratio to nivolumab, 240 mg in 30-minute intravenous infusion on day 1 of a 14-day cycle, or to placebo. Treatment was administered until disease progression, unacceptable toxicity, treatment withdrawal, or 12 months.
The co-primary end points were OS and investigator-reported progression-free survival (PFS). The results were also stratified by epithelioid versus nonepithelioid histology.
At this presentation, the OS data were immature. After a median follow-up of 17.1 months in the nivolumab arm and 14.2 months in the placebo arm, the median OS in patients who received nivolumab was 9.2 months compared with 6.6 months with placebo, a significant difference (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55-0.94; P = .018).
The 12-month survival was 39.5% with nivolumab (95% CI, 32.5-46.3) and 26.9% in the placebo group
(95% CI, 18.2-36.4). The investigator-assessed PFS was also significantly longer with nivolumab versus placebo (3.0 months vs 1.8 months, respectively; HR, 0.61; 95% CI, 0.48-0.77; P <.001). The 12-month PFS was 14.5% in the nivolumab group and 4.9% in the placebo group.
Analysis of the results in 234 tumors based on PD-L1 tumor status revealed that the PD-L1 biomarker does not predict survival for patients who receive nivolumab therapy. The median OS was 8.0 months and 8.7 months, respectively, in nivolumab- and placebo-treated patients who had PD-L1–positive tumors (P = .864). In patients with PD-L1–negative tumors, the median OS was 9.0 months with nivolumab and 6.4 months with placebo (P = .115).
The analysis according to histology stratification showed a significant median OS benefit in the epithelioid group (9.4 months with nivolumab vs 6.6 months with placebo; P = .021), but not in the nonepithelioid group (5.9 months vs 6.7 months; P = .572).
Adverse events were similar between the treatment groups; grade 3 or 4 events were 36% in the nivolumab group and 39% in the placebo group. Treatment discontinuation because of adverse events was 13.1% in the nivolumab group versus 2.7% with placebo. The safety profile of nivolumab, Dr Fennell noted, was consistent with its known profile, with no new safety signals.
“CONFIRM met its end point of statistically improved investigator-reported PFS and OS with nivolumab versus placebo in relapsed malignant mesothelioma,” Dr Fennell said. “Nivolumab is a safe and effective treatment and should be considered a new treatment option for relapsed mesothelioma,” he added.
CONFIRM co-investigator Gareth Griffiths, BSc, MSc, PhD, Director, Southampton Clinical Trials Unit, University of Southampton, England, stated, “CONFIRM gives good evidence that this treatment approach should be considered for the new standard of care for these patients.”