Duration of Targeted Therapy in Patients With Advanced Non–small-cell Lung Cancer Identified by Circulating Tumor DNA Analysis

• Published in: Clinical lung cancer 2020-11, Vol.21 (6), p.545-552.e1
• Main Authors: Reckamp, Karen L., Patil, Tejas, Kirtane, Kedar, Rich, Thereasa A., Espenschied, Carin R., Weipert, Caroline M., Raymond, Victoria M., Santana-Davila, Rafael, Doebele, Robert C., Baik, Christina S.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - pathology; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - antagonists & inhibitors; Biomarkers, Tumor - genetics; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Circulating Tumor DNA - analysis; Circulating Tumor DNA - genetics; Female; Follow-Up Studies; Genotype directed therapy; Humans; Liquid biopsy; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Molecular Targeted Therapy; Oncogene; Prognosis; Retrospective Studies; Survival Rate; Time Factors
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2020.06.015

Outcomes of therapy targeting molecular driver alterations detected in advanced non–small-cell lung (NSCLC) using circulating tumor DNA (ctDNA) have not been widely reported in patients who are targeted therapy-naive. We performed a multicenter retrospective review of patients with unresectable stage IIIB to IV NSCLC who received matched therapy after a targetable driver alteration was identified using a commercial ctDNA assay through usual clinical care. Eligible patients must not have received targeted therapy prior to ctDNA testing (prior chemotherapy or immunotherapy was permitted). Kaplan-Meier analysis was used to estimate the median duration of targeted therapy. Patients still on targeted therapy were censored at last follow-up. Seventy-six patients met inclusion criteria. The median age of diagnosis of NSCLC was 64.5 years (range, 31-87 years), 67% were female, 74% were never-smokers, and 97% had adenocarcinoma histology. Twenty-one (28%) patients received systemic treatment prior to targeted therapy, including chemotherapy (n = 17), immunotherapy (n = 5), and/or a biologic (n = 4). Thirty-three (43%) patients remain on targeted therapy at the time of data analysis. The median time on targeted therapy was similar to what has been reported for tissue-detected oncogenic driver mutations in the targeted therapy-naive setting. Patients with ctDNA-detected drivers had durable time on targeted therapy. These treatment outcomes data compliment previous studies that have shown enhanced targetable biomarker discovery rates and high tissue concordance of ctDNA testing when incorporated at initial diagnosis of NSCLC. Identification of NSCLC driver mutations using well-validated ctDNA assays can be used for clinical decision-making and targeted therapy assignment. Identifying targetable genomic driver alterations is critical for optimal treatment selection in advanced non–small-cell lung cancer (NSCLC). Previous studies have shown that circulating tumor DNA testing increases the identification of informative biomarkers at initial diagnosis. In this study, we show that patients with drivers detected by a validated circulating tumor DNA next-generation sequencing assay had durable times on targeted therapy, comparable with what has been reported for tissue-detected drivers in the targeted therapy-naive setting.