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Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing

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Title: Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing
Authors: Heidi J. Gray, Payel Chatterjee, Rachele Rosati, Lauren R. Appleyard, Grace J. Durenberger, Robert L. Diaz, Hallie A. Swan, Danielle Peretti, Maddy Pollastro, Trevor Ainge, Katannya Kapeli, Shalini Pereira, Astrid L. Margossian, Kalyan Banda, Barbara A. Goff, Elizabeth M. Swisher, Brady Bernard, Christopher J. Kemp, Carla Grandori
Source: npj Precision Oncology, Vol 7, Iss 1, Pp 1-6 (2023)
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Abstract Low-grade serous ovarian cancer (LGSOC) typically responds poorly to standard platinum-based chemotherapy and new therapeutic approaches are needed. We describe a remarkable response to targeted therapy in a patient with platinum-resistant, advanced LGSOC who had failed standard-of-care chemotherapy and two surgeries. The patient was in rapid decline and entering hospice care on home intravenous (i.v.) opioid analgesics and a malignant bowel obstruction requiring a G-tube. Genomic analysis of the patient’s tumor did not indicate obvious therapeutic options. In contrast, a CLIA-certified drug sensitivity assay of an organoid culture derived from the patient’s tumor identified several therapeutic choices, including Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, as well as the EGFR inhibitors afatinib and erlotinib. Following off-label administration of daily ibrutinib as monotherapy, the patient had an exceptional clinical turnaround over the following 65 weeks with normalization of CA-125 levels, resolution of the malignant bowel obstruction, halting of pain medications, and improvement of performance status from ECOG 3 to ECOG 1. After 65 weeks of stable disease, the patient’s CA-125 levels began to rise, at which point the patient discontinued ibrutinib and began taking afatinib as monotherapy. The patient’s CA-125 levels remained stable for an additional 38 weeks but due to anemia and rising CA-125 levels, the patient switched to erlotinib and is currently being monitored. This case highlights the clinical utility of ex vivo drug testing of patient-derived tumor organoids as a new functional precision medicine approach to identify effective personalized therapies for patients who have failed standard-of-care treatments.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2397-768X
Relation: https://doaj.org/toc/2397-768X
DOI: 10.1038/s41698-023-00379-8
Access URL: https://doaj.org/article/8a9cc59b3ce64630836df3b6b10cdaf8
Accession Number: edsdoj.8a9cc59b3ce64630836df3b6b10cdaf8
Database: Directory of Open Access Journals
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  Data: Abstract Low-grade serous ovarian cancer (LGSOC) typically responds poorly to standard platinum-based chemotherapy and new therapeutic approaches are needed. We describe a remarkable response to targeted therapy in a patient with platinum-resistant, advanced LGSOC who had failed standard-of-care chemotherapy and two surgeries. The patient was in rapid decline and entering hospice care on home intravenous (i.v.) opioid analgesics and a malignant bowel obstruction requiring a G-tube. Genomic analysis of the patient’s tumor did not indicate obvious therapeutic options. In contrast, a CLIA-certified drug sensitivity assay of an organoid culture derived from the patient’s tumor identified several therapeutic choices, including Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, as well as the EGFR inhibitors afatinib and erlotinib. Following off-label administration of daily ibrutinib as monotherapy, the patient had an exceptional clinical turnaround over the following 65 weeks with normalization of CA-125 levels, resolution of the malignant bowel obstruction, halting of pain medications, and improvement of performance status from ECOG 3 to ECOG 1. After 65 weeks of stable disease, the patient’s CA-125 levels began to rise, at which point the patient discontinued ibrutinib and began taking afatinib as monotherapy. The patient’s CA-125 levels remained stable for an additional 38 weeks but due to anemia and rising CA-125 levels, the patient switched to erlotinib and is currently being monitored. This case highlights the clinical utility of ex vivo drug testing of patient-derived tumor organoids as a new functional precision medicine approach to identify effective personalized therapies for patients who have failed standard-of-care treatments.
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