dc.contributor.author | Horn, Leora | |
dc.date.accessioned | 2020-04-10T15:04:03Z | |
dc.date.available | 2020-04-10T15:04:03Z | |
dc.date.issued | 2019-04-20 | |
dc.identifier.citation | Ready N, Hellmann MD, Awad MM, et al. First-Line Nivolumab Plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers. J Clin Oncol 2019;37:992-1000 doi:10.1200/JCO.18.01042 [Published Online First:20 Feb 2019]. | en_US |
dc.identifier.issn | 0732-183X | |
dc.identifier.uri | https://ir.vanderbilt.edu/xmlui/handle/1803/9911 | |
dc.description | Only Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://ascopubs.org/doi/pdf/10.1200/JCO.18.01042 | en_US |
dc.description.abstract | PURPOSE CheckMate 568 is an open-label phase II trial that evaluated the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line treatment of advanced/metastatic non-small-cell lung cancer (NSCLC). We assessed the association of efficacy with programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB).
PATIENTS AND METHODS Two hundred eighty-eight patients with previously untreated, recurrent stage IIIB/IV NSCLC received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary end point was objective response rate (ORR) in patients with 1% or more and less than 1% tumor PD-L1 expression. Efficacy on the basis of TMB (FoundationOne CDx assay) was a secondary end point.
RESULTS Of treated patients with tumor available for testing, 252 patients (88%) of 288 were evaluable for PD-L1 expression and 98 patients (82%) of 120 for TMB. ORR was 30% overall and 41% and 15% in patients with 1% or greater and less than 1% tumor PD-L1 expression, respectively. ORR increased with higher TMB, plateauing at 10 or more mutations/megabase (mut/Mb). Regardless of PD-L1 expression, ORRs were higher in patients with TMB of 10 or more mut/Mb (n = 48: PD-L1, >= 1%, 48%; PD-L1, < 1%, 47%) versus TMB of fewer than 10 mut/Mb (n = 50: PD-L1, >= 1%, 18%; PD-L1, < 1%, 5%), and progression-free survival was longer in patients with TMB of 10 or more mut/Mb versus TMB of fewer than 10 mut/Mb (median, 7.1 v 2.6 months). Grade 3 to 4 treatment-related adverse events occurred in 29% of patients.
CONCLUSION Nivolumab plus low-dose ipilimumab was effective and tolerable as a first-line treatment of advanced/metastatic NSCLC. TMB of 10 or more mut/Mb was associated with improved response and prolonged progression-free survival in both tumor PD-L1 expression 1% or greater and less than 1% subgroups and was thus identified as a potentially relevant cutoff in the assessment of TMB as a biomarker for first-line nivolumab plus ipilimumab. (C) 2019 by American Society of Clinical Oncology | en_US |
dc.description.sponsorship | Funded by Bristol-Myers Squibb, (Princeton, NJ) and ONO Pharmaceutical (Osaka, Japan). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Journal of Clinical Oncology | en_US |
dc.rights | Creative Commons Attribution Non-Commercial No Derivatives 4.0 License | |
dc.source.uri | https://ascopubs.org/doi/pdf/10.1200/JCO.18.01042 | |
dc.subject | OPEN-LABEL | en_US |
dc.subject | STAGE IV | en_US |
dc.subject | LANDSCAPE | en_US |
dc.subject | BLOCKADE | en_US |
dc.subject | PD-1 | en_US |
dc.subject | MULTICENTER | en_US |
dc.subject | DOCETAXEL | en_US |
dc.title | First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1200/JCO.18.01042 | |