Prevalence of programmed death ligand-1 (PD-L1) by demographic, disease and sample characteristics in unresectable, stage III NSCLC (PACIFIC)
Authors: D. Planchard, M.C. Garassino, L. Paz-Ares, C. Faivre-Finn, A. Spira, Y. Gu, C. Wadsworth, J. Whiteley, M. Scott, A.-M. Boothman, M. Ratcliffe, J. Walker, P.A. Dennis, S.J. Antonia
Journal: Annals of Oncology (2019)

Background: PACIFIC (NCT02125461) was a randomised, placebo-controlled, phase 3 trial evaluating the immune checkpoint inhibitor durvalumab in patients (pts) with unresectable, Stage III non-small cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy (cCRT). Both primary endpoints of progression-free survival and overall survival were met and significantly improved with durvalumab, with similar safety, versus placebo (Antonia et al, NEJM 2017; 2018). We report exploratory analyses of the prevalence of tumour PD-L1 expression by baseline pt, disease and sample characteristics and by response to prior treatment for pts in PACIFIC. Methods: If available (provision of formalin-fixed paraffin-embedded tumour resection or biopsy samples was optional), archived pre-cCRT tumour tissue was tested retrospectively for PD-L1 tumour cell (TC) expression using the VENTANA PD-L1 (SP263) immunohistochemistry assay and scored at validated pre-specified (≥25%) and post-hoc (≥1%) cutoffs. Overall PD-L1 prevalence (regardless of treatment arm) was summarised by pt subgroups defined by various characteristics, and assessed using a Pearson's chi-squared test for between-group differences. Results: Of 713 randomized pts, 451 (63.2%) were evaluable for PD-L1 status. Among PD-L1-evaluable pts, 67.2% (303/451) had TC ≥ 1% and 35.3% (159/451) had TC ≥ 25% (similar to previous reports in metastatic NSCLC). PD-L1 prevalence by various characteristics at the TC ≥ 1% cut-off are reported in the table.Table85OPatient/disease/sample characteristicSubgroupPrevalence of PD-L1 TC ≥1%, % (n/N)P valueRaceWhite67.5 (206/305)0.5882Black or African American81.8 (9/11)Asian66.4 (85/128)Other50.0 (3/6)RegionAsia64.3 (74/115)0.2642Europe64.9 (124/191)North America and South America72.4 (105/145)Patient age (years)<6566.5 (167/251)0.7418≥6568.0 (136/200)Smoking statusSmoker66.8 (276/413)0.5956Non-smoker71.1 (27/38)SexMale65.3 (209/320)0.1858Female71.8 (94/131)HistologySquamous64.9 (150/231)0.2973Non-squamous69.5 (153/220)Disease stageIIIA69.2 (166/240)0.5029IIIB66.2 (131/198)ECOG/WHO performance statusNormal activity (0)65.8 (150/228)0.5236Restricted activity (1)68.6 (153/223)EGFR statusPositive67.7 (21/31)0.1176Negative68.6 (264/385)Unknown51.4 (18/35)Best response to prior therapyComplete response41.7 (5/12)0.1611Partial response67.7 (151/223)Stable disease68.1 (143/210)Biopsy sample locationLung67.0 (209/312)0.8045Lymph node(s)65.6 (63/96)Specimen typeFormalin-fixed paraffin-embedded block69.2 (126/182)0.4461Unstained slides65.8 (175/266)Collection methodBiopsy68.2 (279/409)0.5879Resection63.6 (21/33)Age of biopsy sample≤90 days73.3 (88/120)0.0902>90 days64.8 (214/330) Open table in a new tab Conclusions: There were no important differences noted in PD-L1 prevalence between relevant subgroups at the TC ≥ 1% or TC ≥ 25% cut-offs (latter data to be presented). PD-L1 status was unaffected by sample type or age or biopsy location, suggesting expression is stable from pre-cCRT diagnostic biopsies, and supports the use of either primary tumour or lymph node biopsies for PD-L1 testing. Clinical trial identification: NCT02125461. Editorial acknowledgement: Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the submitted work. M.C. Garassino: Personal fees: AstraZemeca, Roche, BMS, MSD outside the conduct of this study. L. Paz-Ares: Advisory board fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merk, Boehringer Ingelheim. C. Faivre-Finn: Research funding:AstraZeneca, MSD. A. Spira: Advisory fees, institutional research support: AstraZeneca. Y. Gu, J. Whiteley, M. Scott, J. Walker: Employment, stock: AstraZeneca. C. Wadsworth, P.A. Dennis: Employment, stock: AstraZeneca, outside the conduct of the study. A-M. Boothman: Employment, stock options: AstraZeneca, outside the conduct of the study. M. Ratcliffe: Consultant fees: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.