Outcomes with durvalumab by tumour PD-L1 expression in unresectable, Stage III non-small-cell lung cancer in the PACIFIC trial
Mené sur 709 patients atteints d’un cancer du poumon non à petites cellules de stade III, non résécable et n’ayant pas progressé après une chimioradiothérapie, cet essai randomisé évalue l’efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité du durvalumab, selon l’expression tumorale de PD-L1 (durée médiane de suivi : 33,3 mois)
Background : 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 and Methods : 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). Results : 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. Conclusions : 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.
Annals of Oncology 2020