Circulating Tumor DNA Kinetics Predict Progression-Free and Overall Survival in EGFR TKI–Treated Patients with EGFR-Mutant NSCLC (SWOG S1403)

Philip C. Mack, Jieling Miao, Mary W. Redman, James Moon, Sarah B. Goldberg, Roy S. Herbst, Mary Ann Melnick, Zenta Walther, Fred R. Hirsch, Katerina Politi, Karen Kelly, David R. Gandara

Research output: Contribution to journalArticlepeer-review

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Abstract

Purpose: Dynamic changes in circulating tumor DNA (ctDNA) decreased risk of progression, compared with those with persistent are under investigation as an early indicator of treatment outcome. ctDNA at Cycle 3 Day 1 [HR, 0.23; 95% confidence interval (CI), Experimental Design: Serial plasma ctDNA (baseline, 8 weeks, 0.12–0.45; P < 0.0001], with a median progression-free survival and at progression) was prospectively incorporated into the SWOG (PFS) of 15.1 (95% CI, 10.6–17.5) months in the group with S1403 clinical trial of afatinib ± cetuximab in tyrosine kinase clearance of ctDNA versus 4.6 (1.7–7.5) months in the group with inhibitor—naïve, EGFR mutation tissue–positive non–small cell persistent ctDNA. Clearance was also associated with a decreased risk lung cancer. of death (HR, 0.44; 95% CI, 0.21–0.90), P ¼ 0.02; median overall Results: EGFR mutations were detected in baseline ctDNA survival (OS): 32.6 (23.5–not estimable) versus 15.6 (4.9–28.3) months. in 77% (82/106) of patients, associated with the presence of brain Conclusions: Plasma clearance of mutant EGFR ctDNA at and/or liver metastases and M1B stage. Complete clearance of EGFR 8 weeks was highly and significantly predictive of PFS and OS, mutations in ctDNA by 8 weeks was associated with a significantly outperforming RECIST response for predicting long-term benefit.

Original languageEnglish
Pages (from-to)3752-3760
Number of pages9
JournalClinical Cancer Research
Volume28
Issue number17
DOIs
StatePublished - 1 Sep 2022
Externally publishedYes

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