التفاصيل البيبلوغرافية
| العنوان: |
Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma. |
| المؤلفون: |
Singh, Harshabad, Lowder, Kristen E., Kapner, Kevin, Kelly, Ronan J., Zheng, Hui, McCleary, Nadine Jackson, Abrams, Thomas A., Chan, Jennifer A., Regan, Eileen M., Klempner, Samuel J., Hannigan, Alison M., Remland, Joshua, Brais, Lauren K., Andrews, Elizabeth, Yurgelun, Matthew, Cleary, James M., Rubinson, Douglas A., Ritterhouse, Lauren L., Maron, Garrett, Aguirre, Andrew J. |
| المصدر: |
Nature Communications; 8/9/2024, Vol. 15 Issue 1, p1-15, 15p |
| مصطلحات موضوعية: |
VASCULAR endothelial growth factor antagonists, PROGRESSION-free survival, COOPERATIVE binding (Biochemistry), CIRCULATING tumor DNA, OVERALL survival, BEVACIZUMAB |
| مستخلص: |
Preclinical studies suggest that simultaneous HER2/VEGF blockade may have cooperative effects in gastroesophageal adenocarcinomas. In a single-arm investigator initiated clinical trial for patients with untreated advanced HER2+ gastroesophageal adenocarcinoma, bevacizumab was added to standard of care capecitabine, oxaliplatin, and trastuzumab in 36 patients (NCT01191697). Primary endpoint was objective response rate and secondary endpoints included safety, duration of response, progression free survival, and overall survival. The study met its primary endpoint with an objective response rate of 81% (95% CI 65–92%). Median progression free and overall survival were 14.0 (95% CI, 11.3–36.4) and 23.2 months (95% CI, 16.6–36.4), respectively. The median duration of response was 14.9 months. The regimen was well tolerated without unexpected or severe toxicities. In post-hoc ctDNA analysis, baseline ctDNA features were prognostic: Higher tumor fraction and alternative MAPK drivers portended worse outcomes. ctDNA at resistance identified oncogenic mutations and these were detectable 2–8 cycles prior to radiographic progression. Capecitabine, oxaliplatin, trastuzumab and bevacizumab shows robust clinical activity in HER2+ gastroesophageal adenocarcinoma. Combination of VEGF inhibitors with chemoimmunotherapy and anti-PD1 regimens is warranted. Preclinical studies indicate that simultaneous HER2 and VEGF blockade may be beneficial in gastroesophageal adenocarcinoma (GEA). Here, the authors report the efficacy and biomarker analysis of a phase II clinical trial investigating the combination of bevacizumab (anti-VEGF) and standard-of-care CAPOX (capecitabine, oxaliplatin) and trastuzumab in previously untreated advanced HER2 + GEA. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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