Nivolumab monotherapy significantly prolonged survival vs placebo in patients with relapsed malignant mesothelioma, according to data from a preliminary analysis of the phase 3 CONFIRM trial presented at the 2020 World Conference on Lung Cancer in Singapore.
To date, improved overall survival (OS) has not been achieved in a randomized phase 3 trial for relapsed malignant mesothelioma. Nivolumab has shown benefit in the second-line setting and is currently available in Japan. The CONFIRM trial (NCT03063450) was conducted to assess the efficacy of single-agent nivolumab in a placebo-controlled, phase 3 investigative setting.
CONFIRM investigators randomly assigned 332 patients with mesothelioma who had been treated with at least 1 prior therapy to receive either nivolumab monotherapy (n=221) or placebo (n=111). The coprimary end points were investigator-reported progression-free survival (PFS) and OS. Secondary end points included response rate and safety.
At baseline, the median age was 70 and 71 years in the nivolumab and placebo arms, respectively. Most patients in each group were male (76% vs 77%).
Across the 2 groups, the majority of patients had epithelioid histology (88%). Thirty-seven percent of patients who received nivolumab had a PD-L1 tumor expression level of 1% or greater vs 29% of patients who received placebo. Nivolumab was the second-line treatment for 29% of patients in the immunotherapy arm; it was the third-line therapy for 56%.
Nivolumab was found to significantly prolong OS, with a median of 9.2 months compared with 6.6 months with placebo (HR, 0.72; 95% CI, 0.55-0.94; P =.018). The 12-month OS rate was 39.5% and 26.9% in the nivolumab and placebo groups, respectively.
The OS benefit was primarily observed among patients with epithelioid histology (HR, 0.71; 95% CI, 0.53-0.95; P =.021). There was no improvement in OS in patients with nonepithelioid histology (HR, 0.79; 95% CI, 0.35-1.79; P =.572).
In the overall population, nivolumab also led to prolonged PFS, with a median of 3.0 months compared with 1.8 months with placebo (HR, 0.61; 95% CI, 0.48-0.77; P <.001). The 12-month PFS rate was 14.5% and 4.9% with nivolumab and placebo, respectively.
The rates of any adverse events (AEs) and serious AEs were similar between groups. Grade 3 or higher serious AEs occurred in 36% in the nivolumab group and 39% in the placebo group. There were more deaths due to serious AEs in the placebo group (5.3% vs 3.6%).
The study authors concluded that “nivolumab is a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma.”
Disclosures: Dean Fennell, MBBS, PhD, disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Fennell D, Ottensmeier C, Califano R, et al. Nivolumab versus placebo in relapsed malignant mesothelioma: preliminary results from the CONFIRM phase 3 trial. Presented at: 2020 World Conference on Lung Cancer Singapore; January 28-31, 2020.