Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer Journal Article
| Authors: | Liu, S. Y.; Erazo, T.; Jee, J.; Arfe, A.; Gupta, A.; Pike, L. R. G.; Santini, F. C.; Daly, B.; Schoenfeld, A.; Eichholz, J.; Johnson, K.; Martinez, A.; Sui, J.; Riaz, N.; Chang, J.; Yang, S. R.; Travis, W.; Arcila, M. E.; Guo, J.; Gagne, E.; Garg, K.; Baehner, F.; Lee, N. Y.; Drilon, A.; Kris, M. G.; Scher, H. I.; Razavi, P.; Gomez, D. R.; Jones, D. R.; Rudin, C. M.; Chandarlapaty, S.; Isbell, J. M.; Li, B. T. |
| Article Title: | Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer |
| Abstract: | Introduction: No definitive answers currently exist regarding optimal first-line therapy for HER2-mutant NSCLC. Access to rapid tissue sequencing is a major barrier to precision drug development in the first-line setting. ctDNA analysis has the potential to overcome these obstacles and guide treatment. Methods: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing and received systemic therapy at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx LungTM assay. Primary endpoints were time to the next treatment (TTNT) and overall survival (OS). Results: Sixty-three patients were included in the primary analysis. Chemoimmunotherapy (33/63, 52.4 %) was the predominant first-line treatment with a median TTNT of 5.1 months (95 %CI 4.1 – 6.1) whereas 55.0 % (22/40) of patients who received second-line T-DXd obtained a median TTNT of 9.2 m (95 % CI, 0–22.2). Plasma ctDNA was tested before first-line therapy in 40 patients with a median OS of 28.0 months (95 % CI 21–34), in whom 31 patients (78.0 %) had detectable ctDNA. HER2 mutations were detected on ctDNA with a median turnaround time of 13 days, occasionally co-occurred with EGFR and MET alterations and were tracked longitudinally correlating with treatment response. Patients with detectable baseline ctDNA had significantly shorter OS (hazard ratio (HR), 5.25; 95 % CI, 1.2–23.9; p = 0.019). Conclusion: Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies. © 2024 |
| Keywords: | adult; human tissue; treatment response; aged; unclassified drug; gene mutation; major clinical study; overall survival; bevacizumab; cisplatin; erlotinib; monotherapy; systemic therapy; treatment duration; gemcitabine; cancer patient; antineoplastic agent; ipilimumab; antineoplastic metal complex; etoposide; epidermal growth factor receptor 2; cohort analysis; retrospective study; carcinogenesis; docetaxel; protein tyrosine kinase inhibitor; immunotherapy; targeted therapy; pemetrexed; predictive value; epidermal growth factor receptor kinase inhibitor; neratinib; scatter factor receptor; turnaround time; blood level; non small cell lung cancer; nsclc; second-line treatment; trastuzumab emtansine; first-line treatment; chemoimmunotherapy; cancer prognosis; high throughput sequencing; afatinib; dacomitinib; nivolumab; time to treatment; human; male; female; article; her2 mutation; circulating tumor dna; pembrolizumab; durvalumab; osimertinib; atezolizumab; vinorelbine tartrate; ctdna; antibody drug conjugate; poziotinib; trastuzumab deruxtecan; pyrotinib; t dxd; tarloxotinib |
| Journal Title: | European Journal of Cancer |
| Volume: | 210 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-10-01 |
| Start Page: | 114257 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2024.114257 |
| PUBMED: | 39151324 |
| PROVIDER: | scopus |
| PMCID: | PMC12327952 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Bob T. Li -- Source: Scopus |
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