Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma.

Autor:	Singh H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. harshabad_singh@dfci.harvard.edu.; Harvard Medical School, Boston, MA, USA. harshabad_singh@dfci.harvard.edu., Lowder KE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Kapner K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Kelly RJ; Johns Hopkins Hospital & School of Medicine, Baltimore, MD, USA.; Charles A. Sammons Cancer Center at Baylor University Medical Center, Dallas, TX, USA., Zheng H; Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital, Boston, MA, USA., McCleary NJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Abrams TA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Chan JA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Regan EM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Klempner SJ; Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital, Boston, MA, USA., Hannigan AM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Remland J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Brais LK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Andrews E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Yurgelun M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Cleary JM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Rubinson DA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Ritterhouse LL; Harvard Medical School, Boston, MA, USA.; Center for Integrated Diagnostics, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Maron G; Center for Integrated Diagnostics, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Aguirre AJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA, USA., Meyerhardt JA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Gardecki E; Harvard Medical School, Boston, MA, USA.; Center for Integrated Diagnostics, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Lennerz JK; Harvard Medical School, Boston, MA, USA.; Center for Integrated Diagnostics, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Wolpin BM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Enzinger PC; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. peter_enzinger@dfci.harvard.edu.; Harvard Medical School, Boston, MA, USA. peter_enzinger@dfci.harvard.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 Aug 09; Vol. 15 (1), pp. 6833. Date of Electronic Publication: 2024 Aug 09.
DOI:	10.1038/s41467-024-51271-3
Abstrakt:	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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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