克里唑蒂尼
医学
危险系数
内科学
置信区间
生物标志物
肿瘤科
酪氨酸激酶抑制剂
无进展生存期
胃肠病学
总体生存率
癌症
肺癌
遗传学
生物
恶性胸腔积液
作者
Ross A. Soo,Jean-François Martini,Anthonie J. van der Wekken,Shunsuke Teraoka,Roberto Ferrara,Alice T. Shaw,Deborah Shepard,Anna Maria Calella,A. Polli,Francesca Toffalorio,Pascale Tomasini,Chao‐Hua Chiu,Dariusz M. Kowalski,Hye Ryun Kim,Benjamin J. Solomon
标识
DOI:10.1016/j.jtho.2023.05.021
摘要
Circulating tumor DNA (ctDNA) has been used as a biomarker for prognostication and response to treatment. Here, we evaluate ctDNA as a potential biomarker for response to lorlatinib, a third-generation ALK tyrosine kinase inhibitor in patients with treatment-naive, advanced, ALK-positive NSCLC in the ongoing phase 3 CROWN study (NCT03052608).Molecular responses were calculated using mean variant allele frequency (VAF), longitudinal mean change in VAF (dVAF), and ratio to baseline. Efficacy assessments (progression-free survival [PFS] and objective response rate) were paired with individual patient ctDNA and analyzed for association.Compared with baseline, mean VAF at week 4 was decreased in both treatment arms. Considering all detected somatic variants, a reduction in dVAF (≤0) was associated with a longer PFS in the lorlatinib arm. The hazard ratio (HR) for a dVAF less than or equal to 0 versus more than 0 was 0.50 (95% confidence interval [CI]: 0.23-1.12) in the lorlatinib arm. A similar association was not observed for crizotinib (HR = 1.00, 95% CI: 0.49-2.03). Comparing molecular responders with nonresponders, patients treated with lorlatinib who had a molecular response had longer PFS (HR = 0.37, 95% CI: 0.16-0.85); patients treated with crizotinib who had a molecular response had similar PFS as those without a molecular response (HR = 1.48, 95% CI: 0.67-3.30).In patients with treatment-naive, advanced, ALK-positive NSCLC, early ctDNA dynamics predicted better outcome with lorlatinib but not with crizotinib. These results suggest that ctDNA may be used to monitor and potentially predict efficacy of lorlatinib treatment.
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