Phase II study of avelumab and trastuzumab with FOLFOX chemotherapy in previously untreated HER2-amplified metastatic gastroesophageal adenocarcinoma

Abstract Background Trastuzumab and multiagent chemotherapy have been the standard of care for the 20-30% of metastatic gastric and esophageal adenocarcinomas that overexpress HER2. Preclinical data show that trastuzumab requires a functional adaptive immune system for efficacy, suggesting synergy o...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	The oncologist (Dayton, Ohio) Ročník 30; číslo 7
Hlavní autoři:	Lee, Michael S, Chao, Joseph, Mulcahy, Mary F, Kasi, Pashtoon M, Alistar, Angela T, Mukherjee, Sarbajit, Akce, Mehmet, Moore, Dominic T, McRee, Autumn J, Somasundaram, Ashwin
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	US Oxford University Press 01.07.2025
Témata:	Adenocarcinoma Adenocarcinoma - drug therapy Adenocarcinoma - genetics Adenocarcinoma - pathology Adult Aged Antibodies, Monoclonal, Humanized - administration & dosage Antibodies, Monoclonal, Humanized - pharmacology Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cancer Care and treatment Chemotherapy Clinical Trial Results Drug therapy Esophageal cancer Esophageal Neoplasms - drug therapy Esophageal Neoplasms - genetics Esophageal Neoplasms - pathology Female Fluorouracil - pharmacology Fluorouracil - therapeutic use Humans Leucovorin - pharmacology Leucovorin - therapeutic use Male Middle Aged Organoplatinum Compounds - pharmacology Organoplatinum Compounds - therapeutic use Pharmacology, Experimental Physiological aspects Receptor, ErbB-2 - genetics Stomach cancer Stomach Neoplasms - drug therapy Stomach Neoplasms - genetics Stomach Neoplasms - pathology Trastuzumab - administration & dosage Trastuzumab - pharmacology Trastuzumab - therapeutic use United States trastuzumab esophageal cancer gastric cancer HER2 immunotherapy
ISSN:	1083-7159, 1549-490X, 1549-490X
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Abstract Background Trastuzumab and multiagent chemotherapy have been the standard of care for the 20-30% of metastatic gastric and esophageal adenocarcinomas that overexpress HER2. Preclinical data show that trastuzumab requires a functional adaptive immune system for efficacy, suggesting synergy of trastuzumab combined with immune checkpoint inhibitors, further supported by current clinical studies. Methods HCRN GI17-319 was a multicenter, single-arm, phase II clinical trial with a prespecified 6-subject safety run-in of the anti-PD-L1 antibody avelumab, combined with trastuzumab and mFOLFOX6, in previously untreated, metastatic, HER2-amplified gastric and esophageal adenocarcinomas. The primary endpoint was the best overall response within 24 weeks. Subjects received 9 cycles of induction avelumab, trastuzumab, and mFOLFOX6, followed by maintenance avelumab + trastuzumab. The study was initially designed as a Simon’s 2-stage trial, but enrollment was stopped after the 18-subject first stage for reasons unrelated to safety or efficacy. Results A total of 18 subjects, including the 6-subject safety run-in, were enrolled 4/2019-8/2020. The 24-week response rate was 11/18 (61%; 95% CI: 39%-84%), and the confirmed overall response rate is 9/18 (50%). With a median follow-up of 14.6 months, the median PFS was 8.0 months (95% CI: 5.3-NA) and median OS was 13.1 months (95% CI: 11.5-NA). The regimen was well tolerated, without any new safety signals. Conclusions The combination of avelumab, trastuzumab, and FOLFOX chemotherapy demonstrated some activity, with a reasonable response rate and median PFS. These outcomes provide some support to other clinical trials of similar agents and support the future evaluation of adding avelumab in this setting. NCT03783936.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1083-7159 1549-490X 1549-490X
DOI:	10.1093/oncolo/oyaf195