Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor–Positive Breast Cancer
| العنوان: | Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor–Positive Breast Cancer |
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| المؤلفون: | Junko Tsuji, Tianyu Li, Albert Grinshpun, Tim Coorens, Douglas Russo, Leilani Anderson, Rebecca Rees, Agostina Nardone, Candace Patterson, Niall J. Lennon, Carrie Cibulskis, Ignaty Leshchiner, Nabihah Tayob, Sara M. Tolaney, Nadine Tung, Donald P. McDonnell, Ian E. Krop, Eric P. Winer, Chip Stewart, Gad Getz, Rinath Jeselsohn |
| المصدر: | Clin Cancer Res |
| بيانات النشر: | American Association for Cancer Research (AACR), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Treatment Outcome, Receptors, Estrogen, Oncology, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols, Exome Sequencing, Liquid Biopsy, Humans, Female, Breast Neoplasms, Article |
| الوصف: | Purpose: Sensitivity to endocrine therapy (ET) is critical for the clinical benefit from the combination of palbociclib plus ET in hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer. Bazedoxifene is a third-generation selective estrogen receptor (ER) modulator and selective ER degrader with activity in preclinical models of endocrine-resistant breast cancer, including models harboring ESR1 mutations. Clinical trials in healthy women showed that bazedoxifene is well tolerated. Patients and Methods: We conducted a phase Ib/II study of bazedoxifene plus palbociclib in patients with HR+/HER2− advanced breast cancer who progressed on prior ET (N = 36; NCT02448771). Results: The study met its primary endpoint, with a clinical benefit rate of 33.3%, and the safety profile was consistent with what has previously been seen with palbociclib monotherapy. The median progression-free survival (PFS) was 3.6 months [95% confidence interval (CI), 2.0–7.2]. An activating PIK3CA mutation at baseline was associated with a shorter PFS (HR = 4.4; 95% CI, 1.5–13; P = 0.0026), but activating ESR1 mutations did not impact the PFS. Longitudinal plasma circulating tumor DNA whole-exome sequencing (WES; N = 68 plasma samples) provided an overview of the tumor heterogeneity and the subclonal genetic evolution, and identified actionable mutations acquired during treatment. Conclusions: The combination of palbociclib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pretreated patient population with advanced HR+/HER2− breast cancer. These results merit continued investigation of bazedoxifene in breast cancer. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da4a380680b3c39ba86a4b9cb2d2845eTest https://doi.org/10.1158/1078-0432.ccr-22-2305Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....da4a380680b3c39ba86a4b9cb2d2845e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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