TY - JOUR
T1 - Outcomes with durvalumab by tumour PD-L1 expression in unresectable, stage III non-small-cell lung cancer in the PACIFIC trial
AU - Paz-Ares, L.
AU - Spira, A.
AU - Raben, D.
AU - Planchard, D.
AU - Cho, B. C.
AU - Özgüroğlu, M.
AU - Daniel, D.
AU - Villegas, A.
AU - Vicente, D.
AU - Hui, R.
AU - Murakami, S.
AU - Spigel, D.
AU - Senan, S.
AU - Langer, C. J.
AU - Perez, B. A.
AU - Boothman, A. M.
AU - Broadhurst, H.
AU - Wadsworth, C.
AU - Dennis, P. A.
AU - Antonia, S. J.
AU - Faivre-Finn, C.
N1 - Funding Information:
This study was funded by AstraZeneca ( ClinicalTrials.gov : NCT02125461 ).
Funding Information:
The authors would like to thank the patients, their families and caregivers, and all investigators involved in this study. Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Aaron Korpal, PhD, and Andrew Gannon, MS, MA, of Cirrus Communications (Manchester, UK), an Ashfield company, and was funded by AstraZeneca. Professor Corinne Faivre-Finn is supported by a grant from the National Institute for Health Research Manchester Biomedical Research Centre.
Funding Information:
The authors would like to thank the patients, their families and caregivers, and all investigators involved in this study. Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Aaron Korpal, PhD, and Andrew Gannon, MS, MA, of Cirrus Communications (Manchester, UK), an Ashfield company, and was funded by AstraZeneca. Professor Corinne Faivre-Finn is supported by a grant from the National Institute for Health Research Manchester Biomedical Research Centre. This study was funded by AstraZeneca (ClinicalTrials.gov: NCT02125461). LP-A is a board member of Genomica and has received honoraria from Roche/Genentech, Eli Lilly, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Merck Serono, Pharmamar, Novartis, Celgene, Sysmex, Amgen, and Incyte, and travel, accommodations or expenses from Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol-Myers Squibb, Eli Lilly, and Pfizer; AS has received advisory fees from Array BioPharma and Incyte, honoraria from CytomX Therapeutics, AstraZeneca/MedImmune and Merck, research funding from LAM Therapeutics, and institutional research support from Roche, AstraZeneca/MedImmune, Boehringer Ingelheim, Astellas Pharma, Novartis, NewLink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, TrovaGene, Takeda, MacroGenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Loxo, and Arch Therapeutics; DR has received honoraria from Merck and Nanobiotix, consultant fees from AstraZeneca and Suvica, and advisory board fees from AstraZeneca, Merck, Genentech, and Nanobiotix; DP has received advisory or lecture fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche, honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche, institutional research funding from AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo, and travel, accommodations or expenses from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Merck, Novartis, prIME Oncology, and Pfizer; DD has received institutional research funding from E.R. Squibb and Sons, AstraZeneca, Boehringer Ingelheim, Genentech, Eli Lilly and Company, Novartis Pharmaceuticals, Pfizer, Celgene, and Roche; AV has received honoraria from AstraZeneca, Gilead, and Seattle Genetics; RH has received advisory fees and honoraria from AstraZeneca, Merck Sharp and Dohme, Novartis, Roche, Bristol-Myers Squibb, and Eli Lilly; SS has received research grants from Varian Medical Systems and ViewRay Inc. and honoraria from AstraZeneca, Eli Lilly, Merck Sharp and Dohme, and Celgene; CJL has received honoraria from Roche/Genentech, Eli Lilly, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Novartis, Celgene, Takeda, and Gilead; and travel, accommodations or expenses from Roche, AstraZeneca, Merck Sharp and Dohme, Bristol-Myers Squibb, Eli Lilly and Pfizer; BAP has received advisory fees from AstraZeneca and Bristol-Myers Squibb; and institutional research support from Bristol-Myers Squibb. A-MB and PAD are full-time employees of AstraZeneca with stock ownership; HB is an independent contractor, funded by AstraZeneca; CW was a full-time employee of AstraZeneca when the work was completed; SJA has received advisory fees from Bristol-Myers Squibb, Novartis, Merck, Boehringer Ingelheim, AstraZeneca/MedImmune, Cellular Biomedicine Group, and Memgen; CF-F has received research funding and travel support from Merck, AstraZeneca, and Elekta, and travel support from Pfizer; the remaining authors declare no potential conflicts of interest.
Publisher Copyright:
© 2020
PY - 2020/6
Y1 - 2020/6
N2 - Background: In the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III non-small-cell lung cancer (NSCLC) patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour cell (TC) programmed death-ligand 1 (PD-L1) expression. Patients and methods: Patients were randomly assigned (2:1) to intravenous durvalumab 10 mg/kg 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 cut-offs. Treatment-effect hazard ratios (HRs) were estimated from unstratified Cox proportional hazards models (Kaplan–Meier-estimated medians). Results: In total, 713 patients were randomly assigned, 709 of whom received at least 1 dose of study treatment durvalumab (n = 473) or placebo (n = 236). Some 451 (63%) were PD-L1-assessable: 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 cut-off, 13 February 2017) across all subgroups [HR, 95% confidence interval (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; not reached (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 data cut-off; 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.
AB - Background: In the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III non-small-cell lung cancer (NSCLC) patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour cell (TC) programmed death-ligand 1 (PD-L1) expression. Patients and methods: Patients were randomly assigned (2:1) to intravenous durvalumab 10 mg/kg 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 cut-offs. Treatment-effect hazard ratios (HRs) were estimated from unstratified Cox proportional hazards models (Kaplan–Meier-estimated medians). Results: In total, 713 patients were randomly assigned, 709 of whom received at least 1 dose of study treatment durvalumab (n = 473) or placebo (n = 236). Some 451 (63%) were PD-L1-assessable: 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 cut-off, 13 February 2017) across all subgroups [HR, 95% confidence interval (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; not reached (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 data cut-off; 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.
KW - durvalumab
KW - immunotherapy
KW - non-small-cell lung cancer
KW - PACIFIC
KW - PD-L1 expression
KW - stage III
UR - http://www.scopus.com/inward/record.url?scp=85084203905&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2020.03.287
DO - 10.1016/j.annonc.2020.03.287
M3 - Article
C2 - 32209338
AN - SCOPUS:85084203905
SN - 0923-7534
VL - 31
SP - 798
EP - 806
JO - Annals of Oncology
JF - Annals of Oncology
IS - 6
ER -
