دورية أكاديمية
TIPS-21 PHASE I/II STUDY OF STEREOTACTIC RADIOSURGERY WITH CONCURRENT OLAPARIB FOLLOWED BY ADJUVANT DURVALUMAB AND PHYSICIAN’S CHOICE SYSTEMIC THERAPY IN SUBJECTS WITH BREAST CANCER BRAIN METASTASES (SOLARA)
| العنوان: | TIPS-21 PHASE I/II STUDY OF STEREOTACTIC RADIOSURGERY WITH CONCURRENT OLAPARIB FOLLOWED BY ADJUVANT DURVALUMAB AND PHYSICIAN’S CHOICE SYSTEMIC THERAPY IN SUBJECTS WITH BREAST CANCER BRAIN METASTASES (SOLARA) |
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| المؤلفون: | Shen, Colette, Abdou, Yara, Chen, Linda, Tan, Xianming, Gupta, Gaorav, Lynce, Filipa, Lobbous, Mina, Stringer-Reasor, Erica, Anders, Carey |
| المصدر: | Neuro-Oncology Advances ; volume 5, issue Supplement_3, page iii39-iii39 ; ISSN 2632-2498 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Surgery, Oncology, Neurology (clinical) |
| الوصف: | BACKGROUND Despite progress in the treatment of brain metastasis (BrM) for HER2+ breast cancer (BC), outcomes for patients with HER2-negative BC BrM remain poor. Current standard of care consists of surgery and/or radiotherapy followed by systemic therapy. Preclinical studies show inhibitors of poly(ADP-ribose) polymerase (PARP) are effective together with radiotherapy as DNA damage response inhibitors. Triple-negative BC (TNBC) has higher rates of homologous recombination deficiency compared to other BC subtypes, and together with HER2-negative, BRCA-mutated BC would be particularly sensitive to PARP inhibition. PARP inhibition with immunotherapy has demonstrated promising efficacy in patients with germline BRCA-mutant and metastatic TNBC in clinical trials (MEDIOLA, TOPACIO). In addition, immunotherapy with stereotactic radiosurgery (SRS) is associated with favorable outcomes in patients with BrM. We hypothesize that this biologically-driven combination will enhance local control of SRS-treated BrM through synergy with PARP inhibition, while controlling micrometastatic disease in the brain and extracranial sites by potentiating the immune response. METHODS We are conducting a multi-institution, Phase I/II trial of SRS plus olaparib, followed by durvalumab (with physician’s choice systemic therapy), for patients with TNBC (any BRCA status) or HER2-negative with BRCA-mutated (germline or somatic) BC BrM [NCT04711824]. The primary objectives are to evaluate safety and tolerability (Phase I) and intracranial disease control at 6 months (Phase II). Secondary objectives include assessing intracranial and global progression-free survival, overall survival, and intracranial/extracranial response rate. Exploratory objectives will assess potential biomarkers of treatment response, including changes in circulating tumor cells/DNA in blood and cerebrospinal fluid, germline and tumor mutations in DNA repair pathway genes, and PD-L1 expression, as well as quality of life and patient-reported outcomes. A surgical ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/noajnl/vdad070.151 |
| الإتاحة: | https://doi.org/10.1093/noajnl/vdad070.151Test https://academic.oup.com/noa/article-pdf/5/Supplement_3/iii39/51037592/vdad070.151.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.F02D09B0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/noajnl/vdad070.151 |
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