Center for Thoracic Oncology, The Tisch Cancer Institute, Mount Sinai Health System, New York, New York.
SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Clin Cancer Res. 2022 Sep 1;28(17):3752-3760. doi: 10.1158/1078-0432.CCR-22-0741.
Dynamic changes in circulating tumor DNA (ctDNA) are under investigation as an early indicator of treatment outcome.
Serial plasma ctDNA (baseline, 8 weeks, and at progression) was prospectively incorporated into the SWOG S1403 clinical trial of afatinib ± cetuximab in tyrosine kinase inhibitor-naïve, EGFR mutation tissue-positive non-small cell lung cancer.
EGFR mutations were detected in baseline ctDNA in 77% (82/106) of patients, associated with the presence of brain and/or liver metastases and M1B stage. Complete clearance of EGFR mutations in ctDNA by 8 weeks was associated with a significantly decreased risk of progression, compared with those with persistent ctDNA at Cycle 3 Day 1 [HR, 0.23; 95% confidence interval (CI), 0.12-0.45; P < 0.0001], with a median progression-free survival (PFS) of 15.1 (95% CI, 10.6-17.5) months in the group with clearance of ctDNA versus 4.6 (1.7-7.5) months in the group with persistent ctDNA. Clearance was also associated with a decreased risk of death (HR, 0.44; 95% CI, 0.21-0.90), P = 0.02; median overall survival (OS): 32.6 (23.5-not estimable) versus 15.6 (4.9-28.3) months.
Plasma clearance of mutant EGFR ctDNA at 8 weeks was highly and significantly predictive of PFS and OS, outperforming RECIST response for predicting long-term benefit.
循环肿瘤 DNA（ctDNA）的动态变化正在被研究作为治疗结果的早期指标。
前瞻性地将连续血浆 ctDNA（基线、8 周和进展时）纳入 SWOG S1403 临床试验中，该试验评估了阿法替尼±西妥昔单抗在酪氨酸激酶抑制剂初治、EGFR 突变组织阳性的非小细胞肺癌患者中的疗效。
基线 ctDNA 中检测到 EGFR 突变，在 106 例患者中有 77%（82/106）存在，与脑和/或肝转移和 M1B 期有关。与持续存在 ctDNA 的患者相比，第 8 周 ctDNA 中 EGFR 突变完全清除的患者进展风险显著降低，无进展生存期（PFS）也显著延长[风险比（HR），0.23；95%置信区间（CI），0.12-0.45；P<0.0001]，ctDNA 清除组的中位 PFS 为 15.1（95%CI，10.6-17.5）个月，而持续存在 ctDNA 组的中位 PFS 为 4.6（1.7-7.5）个月。清除也与死亡风险降低相关（HR，0.44；95%CI，0.21-0.90），P=0.02；中位总生存期（OS）：32.6（23.5-无法估计）vs.15.6（4.9-28.3）个月。
第 8 周时血浆中突变 EGFR ctDNA 的清除与 PFS 和 OS 高度显著相关，优于 RECIST 反应预测长期获益。
