Assessing the value of repeat next generation testing in patients with non-small cell lung cancer: A retrospective review.
Authors: Warnecke Brian , Cabal Angelo , Arter Zhaohui , Keshava Hari B. , Harris Jeremy Phillip , Ou Sai-Hong Ignatius , Nagasaka Misako 
Published: June 2024

3071 Background: Analyzing a tumor’s molecular profile in non-small cell lung cancer (NSCLC) by next generation sequencing (NGS) has been essential in the advancement of precision medicine and has led to development of several targeted therapeutic agents. While their use significantly improves patients’ outcomes, patients will inevitably develop progression of disease. Tumor sequencing at the time of progression, whether tissue or liquid biopsy, is important to identify the mechanism of resistance. We sought to investigate which patients benefit from repeat NGS testing which ultimately allowed for changes in their therapeutic management based on its updated molecular profile. Methods: We performed a single institution retrospective study of patients with NSCLC between 2014-2023 who have undergone two or more NGS sequencing. Testing was performed through Foundation One tissue CDx or liquid CDx. Data obtained through chart review included NSCLC stage, NGS dates and results, and treatments received. We evaluated clinically meaningful results from repeat testing if patients were continued on their targeted therapy, were switched to or received additional targeted therapy, detected a target when prior tests were negative, had a change in their systemic therapy, or confirmed recurrence or a second primary. Results: A total of 277 subjects with NSCLC were identified to have had more than one NGS sequencing. The average number of NGS obtained was 2.90. The average number of liquid NGS was 2.15 and tissue based NGS was 0.75. Out of the 277 patients, repeat testing was clinically meaningful in 134 (48%) patients. Of the 134 patients, 67 (50%) harbored EGFR, 16 (11.9%) ALK, 9 (6.7%) KRAS, 6 (4.5%) ROS1, 6 (4.5%) MET exon 14 skipping, 3 (2.2%) ERBB2, 1 (0.7%) BRAF, and 1 (0.7%) RET as their primary driver alteration upon initial testing. 25 patients (18.7%) had other alterations or no alterations. NGS was repeated for early stage localized recurrence in 8 patients (6%), stage I-III who developed new metastasis in 18 patients (13.4%), and recurrent metastasis in 108 patients (80.6%). Of the patients who clinically benefited from repeat testing, 77 patients (57.5%) were continued or resumed on their targeted therapy, 19 (14.2%) were switched to or received additional targeted therapy, 12 (9%) detected a target when prior tests were negative, and 3 (2.2%) had a change in their chemotherapy or immunotherapy. In 23 patients (17.1%), repeat NGS either confirmed recurrence (n=14) or second primary (n=9). Conclusions: Repeat NGS testing in NSCLC can be clinically meaningful to guide management, such as in detecting a target when prior tests were negative, allowing for switch in, continuation of or addition of targeted therapy, or providing confirmation of a recurrence or a second primary. Further research is warranted in this field to evaluate if repeat NGS can ultimately improve clinical outcomes in these patients.