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.
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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.
Reference
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.
