Trastuzumab and Pertuzumab in Patients with Non-Breast/Gastroesophageal HER2-Amplified Tumors: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol J.

Autor:	Connolly RM; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.; Cancer Research @UCC, College of Medicine and Health, University College Cork, Ireland., Wang V; Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, Massachusetts., Hyman DM; Memorial Sloan Kettering Cancer Center, New York, New York., Grivas P; University of Washington, Fred Hutchinson Cancer Center, Seattle, Washington., Mitchell EP; Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania., Wright JJ; Investigational Drug Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland., Sharon E; Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland., Gray RJ; Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, Massachusetts., McShane LM; Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland., Rubinstein LV; Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland., Patton DR; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, Maryland., Williams PM; Frederick National Laboratory for Cancer Research, Frederick, Maryland., Hamilton SR; City of Hope National Medical Center, Duarte, California., Wang J; UT Southwestern Simmons Comprehensive Cancer Center, Dallas, Texas., Wisinski KB; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin., Tricoli JV; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland., Conley BA; Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland., Harris LN; Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland., Arteaga CL; UT Southwestern Simmons Comprehensive Cancer Center, Dallas, Texas., O'Dwyer PJ; University of Pennsylvania, Philadelphia, Pennsylvania., Chen AP; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland., Flaherty KT; Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Apr 01; Vol. 30 (7), pp. 1273-1280.
DOI:	10.1158/1078-0432.CCR-23-0633
Abstrakt:	Purpose: NCI-MATCH assigned patients with advanced cancer and progression on prior treatment, based on genomic alterations in pretreatment tumor tissue. Arm J (EAY131-J) evaluated the combination of trastuzumab/pertuzumab (HP) across HER2-amplified tumors. Patients and Methods: Eligible patients had high levels of HER2 amplification [copy number (CN) ≥7] detected by central next-generation sequencing (NGS) or through NCI-designated laboratories. Patients with breast/gastroesophageal adenocarcinoma and those who received prior HER2-directed therapy were excluded. Enrollment of patients with colorectal cancer was capped at 4 based on emerging data. Patients received HP IV Q3 weeks until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: Thirty-five patients were enrolled, with 25 included in the primary efficacy analysis (CN ≥7 confirmed by a central lab, median CN = 28). Median age was 66 (range, 31-80), and half of all patients had ≥3 prior therapies (range, 1-11). The confirmed ORR was 12% [3/25 partial responses (colorectal, cholangiocarcinoma, urothelial cancers), 90% confidence interval (CI) 3.4%-28.2%]. There was one additional partial response (urothelial cancer) in a patient with an unconfirmed ERBB2 copy number. Median PFS was 3.3 months (90% CI 2.0-4.1), and median OS 9.4 months (90% CI 5.0-18.9). Treatment-emergent adverse events were consistent with prior studies. There was no association between HER2 CN and response. Conclusions: HP was active in a selection of HER2-amplified tumors (non-breast/gastroesophageal) but did not meet the predefined efficacy benchmark. Additional strategies targeting HER2 and potential resistance pathways are warranted, especially in rare tumors. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu