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
Citation:
Ready, N., Hellmann, M.D., Awad, M.M., Otterson, G.A., Gutierrez, M., Gainor, J.F., Borghaei, H., Jolivet, J., Horn, L., Mates, M., Brahmer, J., Rabinowitz, I., Reddy, P.S., Chesney, J., Orcutt, J., Spigel, D.R., Reck, M., O'Byrne, K.J., Paz-Ares, L., Hu, W., Zerba, K., Li, X., Lestini, B., Geese, W.J., Szustakowski, J.D., Green, G., Chang, H., Ramalingam, S.S. 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, Journal of Clinical Oncology, 2019, 37, 12, 992-1000Download Item:
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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.
Author's Homepage:
http://people.tcd.ie/obyrneke
Author: O'Byrne, Ken
Type of material:
Journal ArticleCollections:
Series/Report no:
Journal of Clinical Oncology;37;
12;
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Full text availableKeywords:
Non–small-cell lung cancer (NSCLC), Nivolumab plus, Tumor mutational burden (TMB), Ipilimumab, Trials, Tumor treatmentDOI:
http://dx.doi.org/10.1200/JCO.18.01042Licences: