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Giving the immunotherapy durvalumab for a year after chemoradiotherapy for unresectable stage III lung cancer tripled the time to progression and raised five-year survival from about a third to over 40%.
Double-blind, placebo-controlled phase 3 trial of 713 patients with unresectable stage III NSCLC who had not progressed after concurrent platinum-based chemoradiotherapy, randomised 2:1 to up to 12 months of durvalumab or placebo. Co-primary endpoints were PFS and overall survival.
Median PFS was 16.8 vs 5.6 months (HR 0.52) and overall survival was significantly improved (HR 0.68 in the 2018 report). Five-year OS was 42.9% vs 33.4%. It was the first change in stage III standard of care in two decades and the model for consolidation immunotherapy in small-cell lung cancer (ADRIATIC) and other tumours.
Patients with stage III lung cancer that cannot be removed surgically should receive a year of durvalumab after completing chemoradiotherapy, provided they have not progressed. This roughly doubles the chance of being alive without progression at five years. Whether the benefit extends to PD-L1-negative tumours is contested, and the EGFR-mutated subgroup is better served by osimertinib (LAURA).
Stage III lung cancer is now treated by genotype as well as by stage: an EGFR mutation moves a patient from durvalumab consolidation to osimertinib consolidation. It is also the strongest hazard ratio in the lung cancer literature, which is a reason to read the overall survival data carefully when they arrive.
The current standard for unresectable stage III lung cancer, and the clearest evidence in the disease that consolidation immunotherapy converts responses into cures for some patients rather than merely delaying relapse.
Shares Byoung Chul Cho, Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer, Standard of care, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch.
Shares Immune-related adverse events (irAEs), Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, Progression-free survival (PFS), Overall survival (OS).
Shares PACIFIC, Unresectable stage III non-small-cell lung cancer, Durvalumab, PD-L1.
Shares Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, No one can predict who responds to immunotherapy, Durvalumab, PD-L1.
Shares PACIFIC, Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer, New England Journal of Medicine.
Shares Unresectable stage III non-small-cell lung cancer, Durvalumab, AstraZeneca, Platinum agents.
Shares No one can predict who responds to immunotherapy, Durvalumab, PD-L1, AstraZeneca.
Shares Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC, Unresectable stage III non-small-cell lung cancer, AstraZeneca, Lung cancer (all types).