医学
内科学
肿瘤科
队列
置信区间
免疫疗法
黑色素瘤
彭布罗利珠单抗
联合疗法
癌症
癌症研究
作者
Gabriela Marsavela,Jenny H. Lee,Leslie Calapre,Stephen Q. Wong,Michelle R. Pereira,Ashleigh C. McEvoy,Anna L. Reid,Cleo Robinson,Lydia Warburton,Afaf Abed,Muhammad A. Khattak,Tarek Meniawy,Sarah-Jane Dawson,Shahneen Sandhu,Matteo S. Carlino,Alexander M. Menzies,Richard A. Scolyer,Georgina V. Long,Benhur Amanuel,Michael Millward,Melanie Ziman,Helen Rizos,Elin S. Gray
标识
DOI:10.1158/1078-0432.ccr-20-2251
摘要
Abstract Purpose: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment. Experimental Design: Plasma circulating tumor DNA (ctDNA) was quantified in 125 samples collected from 110 patients prior to commencing treatment with immune checkpoint inhibitors (ICIs), as first- (n = 32) or second-line (n = 27) regimens, or prior to commencing first-line BRAF/MEK inhibitor therapy (n = 66). An external validation cohort included 128 patients commencing ICI therapies in the first- (N = 77) or second-line (N = 51) settings. Results: In the discovery cohort, low ctDNA (≤20 copies/mL) prior to commencing therapy predicted longer progression-free survival (PFS) in patients treated with first-line ICIs [HR, 0.20; 95% confidence interval (CI) 0.07–0.53; P < 0.0001], but not in the second-line setting. An independent cohort validated that ctDNA is predictive of PFS in the first-line setting (HR, 0.42; 95% CI, 0.22–0.83; P = 0.006), but not in the second-line ICI setting. Moreover, ctDNA prior to commencing ICI treatment was not predictive of PFS for patients pretreated with BRAF/MEK inhibitors in either the discovery or validation cohorts. Reduced PFS and overall survival were observed in patients with high ctDNA receiving anti–PD-1 monotherapy, relative to those treated with combination anti–CTLA-4/anti–PD-1 inhibitors. Conclusions: Pretreatment ctDNA is a reliable indicator of patient outcome in the first-line ICI treatment setting, but not in the second-line ICI setting, especially in patients pretreated with BRAF/MEK inhibitors. Preliminary evidence indicated that treatment-naïve patients with high ctDNA may preferentially benefit from combined ICIs.
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