National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong.
Lung Cancer. 2022 Jan;163:14-18. doi: 10.1016/j.lungcan.2021.11.010. Epub 2021 Nov 25.
Response Evaluation Criteria in Solid Tumors (RECIST) has limitations but remains the conventional approach for tumor assessments. We explored whether circulating tumor DNA (ctDNA) can be incorporated into RECIST to provide a more robust measure of tumor response in advanced EGFR-mutant NSCLC.
In FASTACT-2, patients with advanced NSCLC received platinum/gemcitabine intercalated with erlotinib or placebo. EGFR mutation (tumor and plasma ctDNA) was detected using cobas v2. Patients selected for this hypothesis-generating analysis had EGFR mutations (on either tumor or plasma) at baseline and evaluable week 8 plasma EGFR. Week 8 ctDNA and radiologic response status were correlated with survival using landmark cox regression analyses.
Of the original 451 patients, 86 (19.1%) were eligible for this analysis. 73% (n = 63) had detectable ctDNA at baseline. At week 8, 40% (n = 34) had radiologic partial response (PR), 60% (n = 52) had stable disease (SD); 80% (n = 69) had a ctDNA response (undetectable ctDNA). In patients who had initial PR and undetectable ctDNA, 93% (28/30) had ongoing PR subsequently at week 16. The median duration of response was 14.9 months. In patients with SD and undetectable ctDNA at week 8, 28% had radiological PR at week 16. Amongst those with PR at week 8, survival outcomes for those with undetectable vs detectable ctDNA were not statistically significant (PFS HR 0.49, 95%CI 0.16-1.48, p = 0.21; OS HR 0.39, 95%CI 0.13-1.19, p = 0.10). Amongst those with SD at week 8, there was significantly longer survival for those with undetectable vs detectable ctDNA (PFS HR 0.27, 95% CI 0.13-0.57, p < 0.0001; OS HR 0.40, 95% CI 0.20-0.80, p = 0.009).
In patients with SD, undetectable ctDNA at week 8 correlated with survival improvement. Both radiologic and ctDNA responses are prognostic of PFS. Incorporation of ctDNA with RECIST may improve tumor response assessment in EGFR-mutant NSCLC.
实体瘤反应评估标准（RECIST）存在局限性，但仍然是肿瘤评估的常规方法。我们探讨了循环肿瘤 DNA（ctDNA）是否可以纳入 RECIST，以提供更有力的晚期 EGFR 突变型非小细胞肺癌（NSCLC）肿瘤反应测量。
在 FASTACT-2 中，晚期 NSCLC 患者接受铂类/吉西他滨联合厄洛替尼或安慰剂治疗。使用 cobas v2 检测 EGFR 突变（肿瘤和血浆 ctDNA）。对基线和可评估的第 8 周血浆 EGFR 具有 EGFR 突变（肿瘤或血浆）的患者进行了这项假设生成分析。使用 landmark cox 回归分析，将第 8 周 ctDNA 和影像学反应状态与生存相关联。
在最初的 451 名患者中，有 86 名（19.1%）符合本分析条件。73%（n=63）在基线时检测到 ctDNA。在第 8 周时，40%（n=34）有影像学部分缓解（PR），60%（n=52）有疾病稳定（SD）；80%（n=69）有 ctDNA 反应（ctDNA 不可检测）。在最初 PR 和 ctDNA 不可检测的患者中，93%（28/30）在第 16 周时持续 PR。缓解的中位持续时间为 14.9 个月。在第 8 周时 SD 和 ctDNA 不可检测的患者中，有 28%在第 16 周时影像学 PR。在第 8 周时 PR 的患者中，ctDNA 不可检测与可检测患者的生存结果无统计学意义（PFS HR 0.49，95%CI 0.16-1.48，p=0.21；OS HR 0.39，95%CI 0.13-1.19，p=0.10）。在第 8 周时 SD 的患者中，ctDNA 不可检测与更长的生存相关（PFS HR 0.27，95%CI 0.13-0.57，p<0.0001；OS HR 0.40，95%CI 0.20-0.80，p=0.009）。
在 SD 患者中，第 8 周时 ctDNA 不可检测与生存改善相关。影像学和 ctDNA 反应均与 PFS 预后相关。将 ctDNA 与 RECIST 结合可能会改善 EGFR 突变型 NSCLC 的肿瘤反应评估。
