Barlesi F, et al. - In patients with non-small-cell lung cancer (NSCLC) who had already received platinum-based therapy, avelumab (an anti-PD-L1 antibody) was tested for effectiveness and safety. No improvement in overall survival was observed among these patients treated with avelumab vs docetaxel, but avelumab had a favorable safety profile.

Methods

• Researchers performed a multicenter, open-label, randomized, phase 3 trial, (the JAVELIN Lung 200) at 173 hospitals and cancer treatment centers in 31 countries.
• Patients aged 18 years or older and having stage IIIB or IV or recurrent NSCLC and disease progression after treatment with a platinum-containing doublet, an Eastern Cooperative Oncology Group performance status score of 0 or 1, an estimated life expectancy of more than 12 weeks, and adequate hematological, renal, and hepatic function were considered eligible for this trial.
• Either avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m² every 3 weeks was randomly administered (1:1) to participants by using an interactive voice-response system with a stratified permuted block method with variable block length.
• By PD-L1 expression (≥1% vs <1% of tumors cells), which was measured with the 73–10 assay, and histology (squamous vs non-squamous), they stratified randomization.
• Overall survival, analyzed when roughly 337 events (deaths) had occurred in the PD-L1-positive population, was assessed as primary endpoint.
• All PD-L1-positive patients (ie, PD-L1 expression in ≥1% of tumor cells) randomly assigned to study treatment (the primary analysis population) were analyzed to determine the efficacy, which was thereafter assessed in all randomly assigned patients via a hierarchical testing procedure.
• They performed safety analysis in all patients who received at least one dose of study treatment.

Results

• A total of 792 patients were enrolled in this study between March 24, 2015 and January 23, 2017 and were randomly assigned to receive avelumab (n=396) or docetaxel (n=396).
• PD-L1-positive tumors were detected in 264 participants in the avelumab group and 265 in the docetaxel group.
• No significant difference in median overall survival was evident between the avelumab and docetaxel groups among patients with PD-L1-positive tumors (11·4 months [95% CI 9·4–13·9] vs 10·3 months [8·5–13·0]; hazard ratio 0·90 [96% CI 0·72–1·12]; one-sided p=0·16).
• A total of 251 (64%) of 393 avelumab-treated patients and 313 (86%) of 365 docetaxel-treated patients had treatment-related adverse events, including grade 3–5 events in 39 (10%) and 180 (49%) patients, respectively.
• In the avelumab group, the most common grade 3–5 treatment-related adverse events were infusion-related reaction (six patients [2%]) and increased lipase (four [1%]).
• The docetaxel group had neutropenia (51 [14%]), febrile neutropenia (37 [10%]), and decreased neutrophil counts (36 [10%]) as the most commonly documented grade 3–5 treatment-related adverse events.
• In the avelumab group and in the docetaxel group, the serious treatment-related adverse events were experienced by 34 (9%) patients and 75 (21%) patients, respectively.
• Four (1%) participants in the avelumab group died due to treatment-related deaths, two were attributed to interstitial lung disease, one to acute kidney injury, and one was due to a combination of autoimmune myocarditis, acute cardiac failure, and respiratory failure.
• In the docetaxel group, 14 (4%) patients died due to treatment-related deaths, three due to pneumonia, and one each due to febrile neutropenia, septic shock, febrile neutropenia with septic shock, acute respiratory failure, cardiovascular insufficiency, renal impairment, leucopenia with mucosal inflammation and pyrexia, infection, neutropenic infection, dehydration, and unknown causes.