Duration of Targeted Therapy in Patients With Advanced Non-small-cell Lung Cancer Identified by Circulating Tumor DNA
Karen L Reckamp1, Tejas Patil2, Kedar Kirtane3
1Department of Medical Oncology, City of Hope, Duarte, CA.
Background:
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.
Patients And Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Circulating tumor DNA (ctDNA) testing identified targetable mutations in advanced non-small-cell lung cancer (NSCLC) patients. These patients, naive to targeted therapy, showed durable treatment durations, supporting ctDNA use in clinical decision-making.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Limited data exists on outcomes for targeted therapy-naive advanced non-small-cell lung cancer (NSCLC) patients treated based on molecular driver alterations detected by circulating tumor DNA (ctDNA).
- Understanding these outcomes is crucial for integrating ctDNA testing into clinical practice for NSCLC management.
Purpose of the Study:
- To report the treatment outcomes of targeted therapy in advanced NSCLC patients identified with targetable driver alterations using ctDNA.
- To evaluate the duration of targeted therapy in patients who have not previously received such treatment.
Main Methods:
- A multicenter retrospective review was conducted on unresectable stage IIIB to IV NSCLC patients.
- Patients received matched therapy after ctDNA testing identified a targetable driver alteration; prior chemotherapy or immunotherapy was permitted, but not prior targeted therapy.
- Kaplan-Meier analysis estimated the median duration of targeted therapy, with patients still on treatment censored at last follow-up.
Main Results:
- Seventy-six patients met the inclusion criteria, with a median age of 64.5 years; 74% were never-smokers, and 97% had adenocarcinoma.
- Twenty-one percent of patients received prior systemic treatment (chemotherapy, immunotherapy, or biologic).
- Forty-three percent of patients remained on targeted therapy, with a median duration comparable to that seen with tissue-detected mutations in targeted therapy-naive patients.
Conclusions:
- Patients with ctDNA-detected drivers demonstrated durable responses to targeted therapy.
- These findings complement existing data on ctDNA's utility in biomarker discovery and its concordance with tissue testing.
- Validated ctDNA assays can effectively guide clinical decision-making and targeted therapy selection in NSCLC.
