Serial Monitoring of Circulating Tumor DNA by Next-Generation Gene Sequencing as a Biomarker of Response and Survival in Patients With Advanced NSCLC Receiving Pembrolizumab-Based Therapy
| Autor: | Erica L. Carpenter, Stephanie S. Yee, Taylor A. Black, Allysia J. Mak, Austin L. Chien, Jamie Rosenstein, Carin R. Espenschied, Katie Quinn, Rebecca J. Nagy, Benjamin A. Silva, Sharyn I. Katz, Charu Aggarwal, Roger B. Cohen, Corey J. Langer, Aditi P. Singh, Martina I. Lefterova, Jeffrey C. Thompson, Christine Ciunci, Joshua Bauml, Lesli A. Kiedrowski |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Pembrolizumab Antibodies Monoclonal Humanized medicine.disease_cause DNA sequencing Circulating Tumor DNA 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Carcinoma Non-Small-Cell Lung Internal medicine Biomarkers Tumor medicine Humans In patient Lung cancer Aged Neoplasm Staging Aged 80 and over Mutation business.industry High-Throughput Nucleotide Sequencing ORIGINAL REPORTS Middle Aged medicine.disease Progression-Free Survival Survival Rate Treatment Outcome 030104 developmental biology Circulating tumor DNA 030220 oncology & carcinogenesis Biomarker (medicine) Female business |
| Zdroj: | JCO Precis Oncol |
| ISSN: | 2473-4284 |
| Popis: | PURPOSEAlthough the majority of patients with metastatic non–small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in the frontline setting, predicting which patients will experience a durable clinical benefit (DCB) remains challenging.MATERIALS AND METHODSPatients with mNSCLC receiving pembrolizumab monotherapy or in combination with chemotherapy underwent a 74-gene next-generation sequencing panel on blood samples obtained at baseline and at 9 weeks. The change in circulating tumor DNA levels on-therapy (molecular response) was quantified using a ratio calculation with response defined by a > 50% decrease in mean variant allele fraction. Patient response was assessed using RECIST 1.1; DCB was defined as complete or partial response or stable disease that lasted > 6 months. Progression-free survival and overall survival were recorded.RESULTSAmong 67 patients, 51 (76.1%) had > 1 variant detected at a variant allele fraction > 0.3% and thus were eligible for calculation of molecular response from paired baseline and 9-week samples. Molecular response values were significantly lower in patients with an objective radiologic response (log mean 1.25% v 27.7%, P < .001). Patients achieving a DCB had significantly lower molecular response values compared to patients with no durable benefit (log mean 3.5% v 49.4%, P < .001). Molecular responders had significantly longer progression-free survival (hazard ratio, 0.25; 95% CI, 0.13 to 0.50) and overall survival (hazard ratio, 0.27; 95% CI, 0.12 to 0.64) compared with molecular nonresponders.CONCLUSIONMolecular response assessment using circulating tumor DNA may serve as a noninvasive, on-therapy predictor of response to pembrolizumab-based therapy in addition to standard of care imaging in mNSCLC. This strategy requires validation in independent prospective studies. |
| Databáze: | OpenAIRE |
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