As reported in The Lancet Oncology by Barlesi et al, the phase III JAVELIN Lung 200 trial has shown no overall survival benefit with avelumab (Bavencio) vs docetaxel in patients with platinum pretreated programmed cell death ligand 1 (PD-L1)–positive advanced non–small cell lung cancer (NSCLC). Avelumab was associated with fewer severe adverse events.
In the open-label trial, 792 patients with stage IIIB or IV or recurrent NSCLC and disease progression after treatment with a platinum-containing doublet from 173 sites in 31 countries were randomized between March 2015 and January 2017 to receive the anti–PD-L1 antibody avelumab at 10 mg/kg every 2 weeks (n = 396) or docetaxel 75 mg/m2 every 3 weeks (n = 396). Randomization was stratified by PD-L1 expression. A total of 264 patients treated with avelumab and 265 patients treated with docetaxel with PD-L1–positive tumors (expression ≥ 1%) constituted the primary analysis population.
The primary endpoint was overall survival, analyzed when approximately 337 events had occurred in the PD-L1–positive population. Efficacy was to be subsequently analyzed in the entire randomized population in a hierarchical testing procedure.
Median follow-up for overall survival in the PD-L1–positive population was 18.3 months. In the PD-L1–positive population, median overall survival was 11.4 months (95% confidence interval [CI] = 9.4–13.9 months) in the avelumab group vs 10.3 months (95% CI = 8.5–13.0 months) in the docetaxel group (hazard ratio [HR] = 0.90, P = .16). Among all randomized patients, exploratory analysis (due to absence of significance in the primary analysis) showed median overall survival rates of 10.5 months vs 9.9 months (HR = 0.90, nominal P = .12).
In prespecified exploratory analyses, overall survival was improved with avelumab among 168 avelumab and 147 docetaxel patients with PD-L1 expression ≥ 50% (median 13.6 vs 9.2 months, HR = 0.67, P = .0052) and among 120 and 106 patients with expression ≥ 80% (median 17.1 vs 9.3 months, HR = 0.59, P = .0022).
In the PD-L1–positive population, median progression-free survival was 3.4 vs 4.1 months (HR = 1.01, nominal P = .53) in the PD-L1–positive population and 2.8 vs 4.2 months in the full population (HR =1.16, nominal P = .95). After study treatment, 40% of those treated with avelumab and 48% of those treated with docetaxel in the PD-L1–positive population and 40% and 47% in the full population received additional anticancer treatment.
Among all treated patients, treatment-related adverse events of any grade occurred in 64% of the avelumab group vs 86% of the docetaxel group, with grade ≥ 3 adverse events occurring in 10% vs 49%. The most common grade ≥ 3 adverse events were infusion-related reaction (2%) and increased lipase (1%) in the avelumab group and neutropenia (14%), febrile neutropenia (10%), and decreased neutrophil count (10%) in the docetaxel group. Serious treatment-related adverse events occurred in 9% vs 21% of patients, with the most common in the avelumab group being pneumonitis (1%) and interstitial lung disease (1%), and the most common in the docetaxel group being febrile neutropenia (6%), neutropenia (3%), and pneumonia (2%). Treatment-related deaths occurred in four patients in the avelumab group (1%) due to interstitial lung disease in two; acute kidney injury in one; and a combination of autoimmune myocarditis, acute cardiac failure, and respiratory failure in one. Treatment-related deaths occurred in 14 patients in the docetaxel group (4%) due to pneumonia in 3; and febrile neutropenia, septic shock, febrile neutropenia with septic shock, acute respiratory failure, cardiovascular insufficiency, renal impairment, leukopenia with mucosal inflammation and pyrexia, infection, neutropenic infection, dehydration, and unknown causes in 1 patient each, respectively.
The investigators concluded: “Compared with docetaxel, avelumab did not improve overall survival in patients with platinum-treated PD-L1–positive NSCLC, but had a favorable safety profile.”
The study was funded by Merck and Pfizer.
Keunchil Park, MD, of Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, is the corresponding author for The Lancet Oncology article.
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