1. Overall survival was 6.9 months in the placebo group and 10.2 months in the nivolumab group.
2. Progression free survival was 1.8 months in the placebo group and 3.0 in the treatment group.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Malignant mesothelioma is an aggressive and lethal cancer that is most often caused by previous asbestos fibre exposure and new treatments are needed for patients with relapsing malignant mesothelioma. In a small number of patients with this cancer, tumour expression of programmed death-ligand 1 (PD-L1) protein is evident. Poor prognosis has been found in patients with tumours having a high PD-L1 expression. The PD-1 immune checkpoint inhibitor antibody, nivolumab, has demonstrated encouraging clinical activity in previous phase 2 trials. This current study details the outcomes on overall survival (OS), progression-free survival (PFS), 12 month overall survival, and safety of nivolumab as compared to placebo in patients with relapsing malignant mesothelioma who had been previously treated with platinum-based chemotherapy. Median OS was 6.9 months in the placebo group as compared to 10.2 months in the treatment group. Median PFS in the placebo group was 1.8 months, while in the nivolumab group it was 3.0 months. Overall survival at 12 months for patients in the nivolumab group was 43.4% as compared to 30.1% in the placebo group. The most common serious AEs were dyspnea, pneumonia, and respiratory tract infection. Infusion-related reactions and diarrhea were the main AEs leading to treatment discontinuation and only 14% of patients on nivolumab and 3% of patients on placebo discontinued treatment. No treatment-related deaths were recorded for either study group. Limitations of this study include a lack of central radiology review for progression of disease. A further limitation was that the majority of patients admitted into the study were entering third-line treatment, having progressed on both first- and second-line options. As a result, the results from this study may not be directly translated to patients entering the second-line treatment stage. Overall, nivolumab is a potential option in treating patients with relapsed malignant mesothelioma.
Relevant Reading: Novel insights into mesothelioma biology and implications for therapy
In-Depth [randomized controlled trial]: This double-blind, randomized control trial based out of multiple centres in the United Kingdom enrolled 332 patients and randomized them by 2:1 allocation to receive either nivolumab (n=221) or placebo (n=111). Eligibility requirements included adult patients with pleural or peritoneal malignant mesothelioma whose disease had progressed following platinum-based chemotherapy and who had an expected survival of at least 6 months. The effect of nivolumab on overall survival (OS), progression-free survival (PFS), 12-month overall survival, and safety was described. Median OS in the placebo group was 6.9 months (95% confidence interval (CI), 5.0-8.0 months) and 10.2 months in the treatment group (95% CI, 8.5-12.1 months) (adjusted hazard ratio (HR) 0.69 (95% CI, 0.52-0.91), p=0.009). Median PFS was 3.0 months in the nivolumab group (95% CI, 2.8-4.1 months) and 1.8 months in the placebo group (95% CI, 1.4-2.6 months). Overall survival at 12 months in the nivolumab group was 43.4% (95% CI, 36.3-50.4%) and 30.1% in the placebo group (95% CI, 21.0-39.6%). 41% of the treatment group and 44% of the placebo group experienced serious adverse events (AEs) during the trial. The most common serious AEs were dyspnea (8% of nivolumab and 9% of placebo patients), pneumonia (6% of nivolumab and 5% of placebo patients), and respiratory tract infection (4% of nivolumab and 7% of placebo patients). Infusion-related reactions affected 3% of the study group and 2% of the placebo group, while diarrhea was reported in 3% of patients on nivolumab and none of the patients receiving placebo. Gastrointestinal (GI) and skin problems were the most common immune-related AEs, with 34% (GI) and 23% (skin) of patients in the treatment group and 26% (GI) and 13% (skin) of patients in the placebo group affected. Treatment discontinuation was suggested for severe adverse events and only 14% of patients on nivolumab and 3% of patients on placebo discontinued treatment.
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