结直肠癌
帕尼单抗
危险系数
医学
无进展生存期
PTEN公司
叶酸
癌症
肿瘤科
内科学
置信区间
胃肠病学
生物
克拉斯
化疗
PI3K/AKT/mTOR通路
遗传学
细胞凋亡
作者
Arndt Stahler,Andreas J. Kind,Christine Sers,Soulafa Mamlouk,Lothar Müller,M. Karthaus,S. Frühauf,Ullrich Graeven,Ludwig Fischer von Weikersthal,Greta Sommerhäuser,Stefan Kasper,Beeke Hoppe,Annika Kurreck,Swantje Held,Volker Heinemann,David Horst,Armin Jarosch,Sebastian Stintzing,Tanja Trarbach,Dominik Paul Modest
标识
DOI:10.1158/1078-0432.ccr-23-3023
摘要
Abstract Purpose: We evaluated additional mutations in RAS wild-type (WT) metastatic colorectal cancer (mCRC) as prognostic and predictive biomarkers for the efficacy of added panitumumab to a 5-fluorouracil plus folinic acid (FU/FA) maintenance as pre-specified analysis of the randomized PanaMa trial. Patients and Methods: Mutations (MUT) were identified using targeted next-generation sequencing (NGS; Illumina Cancer Hotspot Panel v2) and IHC. RAS/BRAF V600E/PIK3CA/AKT1/ALK1/ERBB2/PTEN MUT and HER2/neu overexpressions were negatively hyperselected and correlated with median progression-free survival (PFS) and overall survival (OS) since start of maintenance treatment, and objective response rates (ORR). Univariate/multivariate Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI). Results: 202 of 248 patients (81.5%) of the full analysis set (FAS) had available NGS data: hyperselection WT, 162 (80.2%); MUT, 40 (19.8%). From start of maintenance therapy, hyperselection WT tumors were associated with longer median PFS as compared with hyperselection MUT mCRC (7.5 vs. 5.4 months; HR, 0.75; 95% CI, 0.52–1.07; P = 0.11), OS (28.7 vs. 22.2 months; HR, 0.53; 95% CI, 0.36–0.77; P = 0.001), and higher ORR (35.8% vs. 25.0%, P = 0.26). The addition of panitumumab to maintenance was associated with significant benefit in hyperselection WT tumors for PFS (9.2 vs. 6.0 months; HR, 0.66; 95% CI, 0.47–0.93; P = 0.02) and numerically also for OS (36.9 vs. 24.9 months; HR, 0.91; 95% CI, 0.61–1.36; P = 0.50), but not in hyperselection MUT tumors. Hyperselection status interacted with maintenance treatment arms in terms of PFS (P = 0.06) and OS (P = 0.009). Conclusions: Extended molecular profiling beyond RAS may have the potential to improve the patient selection for anti-EGFR containing maintenance regimens.
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