Durvalumab Consolidation After Chemoradiotherapy in Stage III NSCLC
As reported by Antonia et al in The New England Journal of Medicine, an interim analysis of the phase III PACIFIC trial showed improved progression-free survival with the programmed cell death protein 1 (PD-1) inhibitor durvalumab (Imfinzi) vs placebo as consolidation in patients with unresectable stage III non–small cell lung cancer (NSCLC) without disease progression after at least two cycles of definitive platinum-based chemoradiation therapy.
Study Details
In the international double-blind trial, 709 patients were randomized 2:1 between May 2014 and April 2016 to receive durvalumab at 10 mg/kg intravenously (IV; n = 473) or IV placebo every 2 weeks (n = 236) for up to 12 months. Randomization was stratified by age, sex, and smoking history. The study drug was administered 1 to 42 days after receipt of chemoradiotherapy. The co-primary endpoints are progression-free survival on blinded independent central review and overall survival (analysis not planned at the time of the current interim analysis). Overall, 69% of patients were white, and 27% were Asian.
Progression-Free Survival
As of data cutoff in February 2017, median follow-up was 14.5 months. Median progression-free survival was 16.8 months in the durvalumab group vs 5.6 months in the placebo group (hazard ratio [HR] = 0.52, P < .001). Progression-free survival rates were 55.9% vs 35.3% at 12 months and 44.2% vs 27.0% at 18 months. The progression-free survival benefit of durvalumab was consistently observed across all prespecified subgroups. Objective response was observed in 28.4% vs 16.0% (P < .001), with 72.8% vs 46.8% of responders having an ongoing response at 18 months. Median distant metastasis–free survival was 23.2 months vs 14.6 months (P < .001).
Adverse Events
Grade 3 or 4 adverse events occurred in 29.9% of the durvalumab group vs 26.1% of the placebo group, with the most common event being pneumonia (4.4% vs 3.8%). Adverse events led to discontinuation of the study drug in 15.4% vs 9.8% of patients. Pneumonitis or radiation pneumonitis of any grade occurred in 33.9% vs 24.8%, and grade 3 or 4 pneumonitis or radiation pneumonitis occurred in 3.4% and 2.6%; pneumonia of any grade occurred in 13.1% vs 7.7%, and grade 3 or 4 pneumonia occurred in 4.4% vs 3.8%.
The investigators concluded: “Progression-free survival was significantly longer with durvalumab than with placebo. The secondary endpoints also favored durvalumab, and safety was similar between the groups.”
The study was funded by AstraZeneca.
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