Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers

被引:1696
|
作者
Goodman, Aaron M. [1 ,2 ,3 ]
Kato, Shumei [1 ,2 ]
Bazhenova, Lyudmila [1 ]
Patel, Sandip P. [1 ]
Frampton, Garrett M. [4 ]
Miller, Vincent [4 ]
Stephens, Philip J. [4 ]
Daniels, Gregory A. [1 ]
Kurzrock, Razelle [1 ,2 ]
机构
[1] Univ Calif San Diego, Dept Med, Div Hematol Oncol, Moores Canc Ctr, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Moores Canc Ctr, Ctr Personalized Canc Therapy, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Dept Med, Moores Canc Ctr, Div Blood & Marrow Transplantat, La Jolla, CA 92093 USA
[4] Fdn Med, Cambridge, MA USA
关键词
DOSE RECOMBINANT INTERLEUKIN-2; PD-1; BLOCKADE; NIVOLUMAB; BIOMARKER; MELANOMA; SURVIVAL; PEMBROLIZUMAB; EXPRESSION; LANDSCAPE;
D O I
10.1158/1535-7163.MCT-17-0386
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Immunotherapy induces durable responses in a subset of patients with cancer. High tumor mutational burden (TMB) may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non-small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. We reviewed data on 1,638 patients who had undergone comprehensive genomic profiling and had TMB assessment. Immuno-therapy-treated patients (N = 151) were analyzed for response rate (RR), progression-free survival (PFS), and overall survival (OS). Higher TMB was independently associated with better outcome parameters (multivariable analysis). The RR for patients with high (>= 20 mutations/mb) versus low to intermediate TMB was 22/38 (58%) versus 23/113 (20%; P = 0.0001); median PFS, 12.8 months vs. 3.3 months (P <= 0.0001); median OS, not reached versus 16.3 months (P = 0.0036). Results were similar when anti-PD-1/PD-L1 monotherapy was analyzed (N = 102 patients), with a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders versus nonresponders treated with anti-PD-1/PD-L1 monotherapy was 18.0 versus 5.0 mutations/mb (P < 0.0001). Interestingly, anti-CTLA4/anti-PD-1/PD-L1 combinations versus anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%; P = 0.004) and PFS (P = 0.024). Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. Benefit from dual checkpoint blockade did not show a similarly strong dependence on TMB. (C) 2017 AACR.
引用
收藏
页码:2598 / 2608
页数:11
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