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

by Selleckchem | Jun 28 2023

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.

Comments:

The passage describes a case study of a patient with low-grade serous ovarian cancer (LGSOC) who did not respond well to standard platinum-based chemotherapy. The patient had undergone multiple surgeries and was in a deteriorating condition, requiring hospice care and experiencing a malignant bowel obstruction. Genomic analysis of the tumor did not provide clear therapeutic options. However, a drug sensitivity assay using an organoid culture derived from the patient's tumor identified several potential treatments, including the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, as well as the EGFR inhibitors afatinib and erlotinib.

The patient was administered off-label treatment with ibrutinib as a monotherapy. Remarkably, the patient experienced significant clinical improvement over the following 65 weeks. The patient's CA-125 levels (a marker for ovarian cancer) normalized, the malignant bowel obstruction resolved, pain medication was no longer required, and the patient's performance status improved. After 65 weeks of stable disease, the patient's CA-125 levels started to rise, leading to the discontinuation of ibrutinib and the initiation of afatinib as monotherapy. The patient's CA-125 levels remained stable for an additional 38 weeks. However, due to anemia and increasing CA-125 levels, the patient switched to erlotinib and is currently under monitoring.

This case study demonstrates the clinical utility of using ex vivo drug testing of patient-derived tumor organoids as a functional precision medicine approach. By analyzing the response of tumor organoids to various drugs, personalized therapies can be identified for patients who have failed standard treatments. This approach allowed for the identification of effective targeted therapies, such as ibrutinib, afatinib, and erlotinib, which resulted in a remarkable clinical turnaround and prolonged stable disease for the patient.