Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer

Abstract 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 funct...

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Autores principales:	Douglas Yee, Claudine Isaacs, Denise M. Wolf, Christina Yau, Paul Haluska, Karthik V. Giridhar, Andres Forero-Torres, A. Jo Chien, Anne M. Wallace, Lajos Pusztai, Kathy S. Albain, Erin D. Ellis, Heather Beckwith, Barbara B. Haley, Anthony D. Elias, Judy C. Boughey, Kathleen Kemmer, Rachel L. Yung, Paula R. Pohlmann, Debu Tripathy, Amy S. Clark, Hyo S. Han, Rita Nanda, Qamar J. Khan, Kristen K. Edmiston, Emanuel F. Petricoin, Erica Stringer-Reasor, Carla I. Falkson, Melanie Majure, Rita A. Mukhtar, Teresa L. Helsten, Stacy L. Moulder, Patricia A. Robinson, Julia D. Wulfkuhle, Lamorna Brown-Swigart, Meredith Buxton, Julia L. Clennell, Melissa Paoloni, Ashish Sanil, Scott Berry, Smita M. Asare, Amy Wilson, Gillian L. Hirst, Ruby Singhrao, Adam L. Asare, Jeffrey B. Matthews, Nola M. Hylton, Angela DeMichele, Michelle Melisko, Jane Perlmutter, Hope S. Rugo, W. Fraser Symmans, Laura J. van‘t Veer, Donald A. Berry, Laura J. Esserman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/784de0fabd374658a9d09088fa4a5ee8
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spelling	oai:doaj.org-article:784de0fabd374658a9d09088fa4a5ee82021-12-02T18:01:52ZGanitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer10.1038/s41523-021-00337-22374-4677https://doaj.org/article/784de0fabd374658a9d09088fa4a5ee82021-10-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00337-2https://doaj.org/toc/2374-4677Abstract 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.Douglas YeeClaudine IsaacsDenise M. WolfChristina YauPaul HaluskaKarthik V. GiridharAndres Forero-TorresA. Jo ChienAnne M. WallaceLajos PusztaiKathy S. AlbainErin D. EllisHeather BeckwithBarbara B. HaleyAnthony D. EliasJudy C. BougheyKathleen KemmerRachel L. YungPaula R. PohlmannDebu TripathyAmy S. ClarkHyo S. HanRita NandaQamar J. KhanKristen K. EdmistonEmanuel F. PetricoinErica Stringer-ReasorCarla I. FalksonMelanie MajureRita A. MukhtarTeresa L. HelstenStacy L. MoulderPatricia A. RobinsonJulia D. WulfkuhleLamorna Brown-SwigartMeredith BuxtonJulia L. ClennellMelissa PaoloniAshish SanilScott BerrySmita M. AsareAmy WilsonGillian L. HirstRuby SinghraoAdam L. AsareJeffrey B. MatthewsNola M. HyltonAngela DeMicheleMichelle MeliskoJane PerlmutterHope S. RugoW. Fraser SymmansLaura J. van‘t VeerDonald A. BerryLaura J. EssermanNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Douglas Yee Claudine Isaacs Denise M. Wolf Christina Yau Paul Haluska Karthik V. Giridhar Andres Forero-Torres A. Jo Chien Anne M. Wallace Lajos Pusztai Kathy S. Albain Erin D. Ellis Heather Beckwith Barbara B. Haley Anthony D. Elias Judy C. Boughey Kathleen Kemmer Rachel L. Yung Paula R. Pohlmann Debu Tripathy Amy S. Clark Hyo S. Han Rita Nanda Qamar J. Khan Kristen K. Edmiston Emanuel F. Petricoin Erica Stringer-Reasor Carla I. Falkson Melanie Majure Rita A. Mukhtar Teresa L. Helsten Stacy L. Moulder Patricia A. Robinson Julia D. Wulfkuhle Lamorna Brown-Swigart Meredith Buxton Julia L. Clennell Melissa Paoloni Ashish Sanil Scott Berry Smita M. Asare Amy Wilson Gillian L. Hirst Ruby Singhrao Adam L. Asare Jeffrey B. Matthews Nola M. Hylton Angela DeMichele Michelle Melisko Jane Perlmutter Hope S. Rugo W. Fraser Symmans Laura J. van‘t Veer Donald A. Berry Laura J. Esserman Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
description	Abstract 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.
format	article
author	Douglas Yee Claudine Isaacs Denise M. Wolf Christina Yau Paul Haluska Karthik V. Giridhar Andres Forero-Torres A. Jo Chien Anne M. Wallace Lajos Pusztai Kathy S. Albain Erin D. Ellis Heather Beckwith Barbara B. Haley Anthony D. Elias Judy C. Boughey Kathleen Kemmer Rachel L. Yung Paula R. Pohlmann Debu Tripathy Amy S. Clark Hyo S. Han Rita Nanda Qamar J. Khan Kristen K. Edmiston Emanuel F. Petricoin Erica Stringer-Reasor Carla I. Falkson Melanie Majure Rita A. Mukhtar Teresa L. Helsten Stacy L. Moulder Patricia A. Robinson Julia D. Wulfkuhle Lamorna Brown-Swigart Meredith Buxton Julia L. Clennell Melissa Paoloni Ashish Sanil Scott Berry Smita M. Asare Amy Wilson Gillian L. Hirst Ruby Singhrao Adam L. Asare Jeffrey B. Matthews Nola M. Hylton Angela DeMichele Michelle Melisko Jane Perlmutter Hope S. Rugo W. Fraser Symmans Laura J. van‘t Veer Donald A. Berry Laura J. Esserman
author_facet	Douglas Yee Claudine Isaacs Denise M. Wolf Christina Yau Paul Haluska Karthik V. Giridhar Andres Forero-Torres A. Jo Chien Anne M. Wallace Lajos Pusztai Kathy S. Albain Erin D. Ellis Heather Beckwith Barbara B. Haley Anthony D. Elias Judy C. Boughey Kathleen Kemmer Rachel L. Yung Paula R. Pohlmann Debu Tripathy Amy S. Clark Hyo S. Han Rita Nanda Qamar J. Khan Kristen K. Edmiston Emanuel F. Petricoin Erica Stringer-Reasor Carla I. Falkson Melanie Majure Rita A. Mukhtar Teresa L. Helsten Stacy L. Moulder Patricia A. Robinson Julia D. Wulfkuhle Lamorna Brown-Swigart Meredith Buxton Julia L. Clennell Melissa Paoloni Ashish Sanil Scott Berry Smita M. Asare Amy Wilson Gillian L. Hirst Ruby Singhrao Adam L. Asare Jeffrey B. Matthews Nola M. Hylton Angela DeMichele Michelle Melisko Jane Perlmutter Hope S. Rugo W. Fraser Symmans Laura J. van‘t Veer Donald A. Berry Laura J. Esserman
author_sort	Douglas Yee
title	Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
title_short	Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
title_full	Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
title_fullStr	Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
title_full_unstemmed	Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
title_sort	ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/784de0fabd374658a9d09088fa4a5ee8
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Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer

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