Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer.
Journal
NPJ breast cancer
ISSN: 2374-4677
Titre abrégé: NPJ Breast Cancer
Pays: United States
ID NLM: 101674891
Informations de publication
Date de publication:
05 Oct 2021
05 Oct 2021
Historique:
received:
23
11
2020
accepted:
26
08
2021
entrez:
6
10
2021
pubmed:
7
10
2021
medline:
7
10
2021
Statut:
epublish
Résumé
I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY's prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.
Identifiants
pubmed: 34611148
doi: 10.1038/s41523-021-00337-2
pii: 10.1038/s41523-021-00337-2
pmc: PMC8492731
doi:
Types de publication
Journal Article
Langues
eng
Pagination
131Subventions
Organisme : NCI NIH HHS
ID : P01 CA210961
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
© 2021. The Author(s).
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