Local Therapy for Isolated Central Nervous System Progression Among Patients Receiving Antibody-Drug Conjugate Therapy

Purpose: Antibody drug conjugates (ADCs) are an increasingly important class of therapeutics among patients with breast, lung, urothelial, and other malignancies. Guidelines recommend local therapy and continuation of current systemic therapy among patients with isolated brain relapse. We describe t...

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Main Authors: Emily S. Lebow, MD, Jordan Eichholz, MS, Zhigang Zhang, PhD, Nicolas Toumbacaris, MSPH, Brandon Imber, MD, MA, Linda Chen, MD, Quincey LaPlant, MD, PhD, Josh Yamada, MD, Luke R.G. Pike, MD, DPhil, Shanu Modi, MD, Andrew D. Seidman, MD, Kathryn Beal, MD, Nelson S. Moss, MD, Yao Yu, MD
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Advances in Radiation Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S2452109425000028
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author Emily S. Lebow, MD
Jordan Eichholz, MS
Zhigang Zhang, PhD
Nicolas Toumbacaris, MSPH
Brandon Imber, MD, MA
Linda Chen, MD
Quincey LaPlant, MD, PhD
Josh Yamada, MD
Luke R.G. Pike, MD, DPhil
Shanu Modi, MD
Andrew D. Seidman, MD
Kathryn Beal, MD
Nelson S. Moss, MD
Yao Yu, MD
author_facet Emily S. Lebow, MD
Jordan Eichholz, MS
Zhigang Zhang, PhD
Nicolas Toumbacaris, MSPH
Brandon Imber, MD, MA
Linda Chen, MD
Quincey LaPlant, MD, PhD
Josh Yamada, MD
Luke R.G. Pike, MD, DPhil
Shanu Modi, MD
Andrew D. Seidman, MD
Kathryn Beal, MD
Nelson S. Moss, MD
Yao Yu, MD
author_sort Emily S. Lebow, MD
collection DOAJ
description Purpose: Antibody drug conjugates (ADCs) are an increasingly important class of therapeutics among patients with breast, lung, urothelial, and other malignancies. Guidelines recommend local therapy and continuation of current systemic therapy among patients with isolated brain relapse. We describe the clinical outcomes of this approach among patients receiving ADCs. Methods and Materials: We queried our institutional database for patients receiving radiation therapy (RT) in the setting of isolated brain progression on ADCs with a plan to continue same-line therapy after radiation. Patients with ≤3 brain metastases at the time of recurrence were categorized as oligoprogressive. Study endpoints included overall survival, progression-free survival (PFS), and the cumulative incidence of next therapy from the start of local therapy. Results: We identified 17 patients receiving ADC therapy with isolated brain progression treated with radiation (stereotactic radiosurgery [SRS]: n = 13, whole brain radiation: n = 4). All patients received concurrent ADC and RT. The median follow-up from local therapy was 29.5 months (95% CI, 21.4-not reached). The median overall survival was 19 months (95% CI, 16-not reached), and the median PFS was 8.1 months (range, 6.7-19 months). One lesion treated with SRS had local failure 21 months after treatment, and the 24-month cumulative incidence of local failure across the entire cohort was 1.6% (95% CI, 0.13%-7.7%). The 6-month cumulative incidence of radiation necrosis was 12% (95% CI, 1.8%-32%). The cumulative incidence of next therapy at 6 and 12 months was 47% (95% CI, 22%-69%) and 71% (95% CI, 41%-87%), respectively, and was significantly lower among patients with oligoprogressive brain recurrence. After SRS, 2 patients were without evidence of disease, discontinued systemic therapy, and were stable on observation at last follow-up. Conclusions: To the best of our knowledge, this is the first clinical report of outcomes using the guideline-recommended approach of local therapy for isolated brain relapse among patients receiving ADCs. Local therapy may delay the need for next line systemic therapy, particularly among patients with oligoprogressive brain relapse.
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spelling doaj-art-e4c4b3fb9d4e4c8cab14b2eb140e59862025-08-20T02:55:04ZengElsevierAdvances in Radiation Oncology2452-10942025-03-0110310171410.1016/j.adro.2025.101714Local Therapy for Isolated Central Nervous System Progression Among Patients Receiving Antibody-Drug Conjugate TherapyEmily S. Lebow, MD0Jordan Eichholz, MS1Zhigang Zhang, PhD2Nicolas Toumbacaris, MSPH3Brandon Imber, MD, MA4Linda Chen, MD5Quincey LaPlant, MD, PhD6Josh Yamada, MD7Luke R.G. Pike, MD, DPhil8Shanu Modi, MD9Andrew D. Seidman, MD10Kathryn Beal, MD11Nelson S. Moss, MD12Yao Yu, MD13Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PennsylvaniaDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Radiation Oncology, Cornell Medical Center, New York, New YorkDepartment of Neurosurgery and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Corresponding author: Yao Yu, MDPurpose: Antibody drug conjugates (ADCs) are an increasingly important class of therapeutics among patients with breast, lung, urothelial, and other malignancies. Guidelines recommend local therapy and continuation of current systemic therapy among patients with isolated brain relapse. We describe the clinical outcomes of this approach among patients receiving ADCs. Methods and Materials: We queried our institutional database for patients receiving radiation therapy (RT) in the setting of isolated brain progression on ADCs with a plan to continue same-line therapy after radiation. Patients with ≤3 brain metastases at the time of recurrence were categorized as oligoprogressive. Study endpoints included overall survival, progression-free survival (PFS), and the cumulative incidence of next therapy from the start of local therapy. Results: We identified 17 patients receiving ADC therapy with isolated brain progression treated with radiation (stereotactic radiosurgery [SRS]: n = 13, whole brain radiation: n = 4). All patients received concurrent ADC and RT. The median follow-up from local therapy was 29.5 months (95% CI, 21.4-not reached). The median overall survival was 19 months (95% CI, 16-not reached), and the median PFS was 8.1 months (range, 6.7-19 months). One lesion treated with SRS had local failure 21 months after treatment, and the 24-month cumulative incidence of local failure across the entire cohort was 1.6% (95% CI, 0.13%-7.7%). The 6-month cumulative incidence of radiation necrosis was 12% (95% CI, 1.8%-32%). The cumulative incidence of next therapy at 6 and 12 months was 47% (95% CI, 22%-69%) and 71% (95% CI, 41%-87%), respectively, and was significantly lower among patients with oligoprogressive brain recurrence. After SRS, 2 patients were without evidence of disease, discontinued systemic therapy, and were stable on observation at last follow-up. Conclusions: To the best of our knowledge, this is the first clinical report of outcomes using the guideline-recommended approach of local therapy for isolated brain relapse among patients receiving ADCs. Local therapy may delay the need for next line systemic therapy, particularly among patients with oligoprogressive brain relapse.http://www.sciencedirect.com/science/article/pii/S2452109425000028
spellingShingle Emily S. Lebow, MD
Jordan Eichholz, MS
Zhigang Zhang, PhD
Nicolas Toumbacaris, MSPH
Brandon Imber, MD, MA
Linda Chen, MD
Quincey LaPlant, MD, PhD
Josh Yamada, MD
Luke R.G. Pike, MD, DPhil
Shanu Modi, MD
Andrew D. Seidman, MD
Kathryn Beal, MD
Nelson S. Moss, MD
Yao Yu, MD
Local Therapy for Isolated Central Nervous System Progression Among Patients Receiving Antibody-Drug Conjugate Therapy
Advances in Radiation Oncology
title Local Therapy for Isolated Central Nervous System Progression Among Patients Receiving Antibody-Drug Conjugate Therapy
title_full Local Therapy for Isolated Central Nervous System Progression Among Patients Receiving Antibody-Drug Conjugate Therapy
title_fullStr Local Therapy for Isolated Central Nervous System Progression Among Patients Receiving Antibody-Drug Conjugate Therapy
title_full_unstemmed Local Therapy for Isolated Central Nervous System Progression Among Patients Receiving Antibody-Drug Conjugate Therapy
title_short Local Therapy for Isolated Central Nervous System Progression Among Patients Receiving Antibody-Drug Conjugate Therapy
title_sort local therapy for isolated central nervous system progression among patients receiving antibody drug conjugate therapy
url http://www.sciencedirect.com/science/article/pii/S2452109425000028
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