Outcomes with durvalumab by tumour PD-L1 expression in unresectable, Stage III non-small-cell lung cancer in the PACIFIC trial.

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In PACIFIC, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, Stage III NSCLC patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour-cell (TC) PD-L1 expression.Patients were randomised (2:1) to durvalumab 10 mg/kg intravenously every-2-weeks or placebo =12 months, stratified by age, sex and smoking history but not PD-L1 status. Where available, pre-CRT samples were tested for PD-L1 expression (immunohistochemistry) and scored at pre-specified (25%) and post-hoc (1%) TC cutoffs. Treatment-effect HRs were estimated from unstratified-Cox-proportional-hazards models (Kaplan-Meier-estimated medians).709/713 randomised patients received durvalumab (n=473) or placebo (n=236). 451 (63%) were PD-L1-evaluable: 35%, 65%, 67%, 33%, and 32% had TC =25%, <25%, =1%, <1%, and 1-24%, respectively. As of 31-January-2019, median follow-up was 33.3 months. Durvalumab improved PFS versus placebo (primary-analysis data cutoff [DCO], 13-February-2017) across all subgroups (HR, 95% CI; medians): TC =25% (0.41, 0.26-0.65; 17.8 versus 3.7 months), <25% (0.59, 0.43-0.82; 16.9 versus 6.9 months), =1% (0.46, 0.33-0.64; 17.8 versus 5.6 months), <1% (0.73, 0.48-1.11; 10.7 versus 5.6 months), 1-24% (0.49, 0.30-0.80; NR versus 9.0 months), and unknown (0.59, 0.42-0.83; 14.0 versus 6.4 months). Durvalumab improved OS across most subgroups (31-January-2019 DCO; HR, 95% CI; medians): TC =25% (0.50, 0.30-0.83; NR versus 21.1 months), <25% (0.89, 0.63-1.25; 39.7 versus 37.4 months), =1% (0.59, 0.41-0.83; NR versus 29.6 months), 1-24% (0.67, 0.41-1.10; 43.3 versus 30.5 months), and unknown (0.60, 0.43-0.84; 44.2 versus 23.5 months), but not <1% (1.14, 0.71-1.84; 33.1 versus 45.6 months). Safety was similar across subgroups.PFS benefit with durvalumab was observed across all subgroups, and OS benefit across all but TC <1%, for which limitations and wide HR CI preclude robust conclusions.


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