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Bintrafusp alfa, an anti-PD-L1:TGF-ß trap fusion protein, in patients with ctDNA-positive, liver-limited metastatic colorectal cancer.
Morris, Van K; Overman, Michael J; Lam, Michael; Parseghian, Christine M; Johnson, Benny; Dasari, Arvind; Raghav, Kanwal; Kee, Bryan K; Huey, Ryan; Wolff, Robert A; Shen, John Paul; Li, June; Zorrilla, Isabel; Tzeng, Ching-Wei D; Tran Cao, Hop S; Chun, Yun Shin; Newhook, Timothy E; Vauthey, Nicolas; Duose, Dzifa; Luthra, Raja; Haymaker, Cara; Kopetz, Scott.
Afiliación
  • Morris VK; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Overman MJ; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Lam M; Department of Medical Oncology and Cancer Services, The University of Melbourne, Australia.
  • Parseghian CM; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Johnson B; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Dasari A; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Raghav K; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Kee BK; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Huey R; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Wolff RA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Shen JP; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Li J; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, USA.
  • Zorrilla I; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Tzeng CD; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Tran Cao HS; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Chun YS; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Newhook TE; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Vauthey N; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, USA.
  • Duose D; Departments of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, USA.
  • Luthra R; Departments of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, USA.
  • Haymaker C; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, USA.
  • Kopetz S; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
Cancer Res Commun ; 2(9): 979-986, 2022 09.
Article en En | MEDLINE | ID: mdl-36382087
ABSTRACT

Background:

Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) CRC, increased TGF-ß signaling results in exclusion of anti-tumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGF-ßRII receptor ("TGF-ß trap") and anti-PD-L1 antibody.

Methods:

Patients with liver-limited, MSS mCRC and with detected ctDNA after complete resection of all known tumors and standard-of-care therapy were treated with 1200 mg of BA intravenously every 14 days for six doses. The primary endpoint was ctDNA clearance. Radiographic characteristics at recurrence were compared using independent t-tests to historical data from a similar cohort of patients with liver-limited mCRC who underwent observation.

Results:

Only 4 of 15 planned patients received BA before the study was stopped early for loss of equipoise. There was no grade ≥3 AE. None of the patients cleared ctDNA. All patients developed radiographic recurrence by the first planned restaging. Although not detectable at prior to treatment, TGFß3 was found in circulation in all patients at cycle 2 day 1. Compared to a historical cohort, patients administered BA developed more metastases (15 versus 2, p=0.005) and greater tumor volumes (9 cm vs 2 cm, p=0.05).

Conclusions:

Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, highlighting the potential context-specific complexity of dual TGF-ß and PD-L1 inhibition.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Asunto principal: Neoplasias del Recto / Neoplasias Colorrectales / Neoplasias del Colon / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Res Commun Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Asunto principal: Neoplasias del Recto / Neoplasias Colorrectales / Neoplasias del Colon / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Res Commun Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos