ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast

Elisa Agostinetto; Guilherme Nader-Marta; Marianne Paesmans; Lieveke Ameye; Isabelle Veys; Laurence Buisseret; Patrick Neven; Donatienne Taylor; Christel Fontaine; Francois P Duhoux; Jean-Luc Canon; Hannelore Denys; Florence Coussy; Camille Chakiba; Joana Mourato Ribeiro; Martine Piccart; Christine Desmedt; Michail Ignatiadis; Philippe Aftimos

doi:10.2217/fon-2022-0358

ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast

Elisa Agostinetto, Guilherme Nader-Marta, Marianne Paesmans, Lieveke Ameye, Isabelle Veys, Laurence Buisseret, Patrick Neven, Donatienne Taylor, Christel Fontaine, Francois P Duhoux, Jean-Luc Canon, Hannelore Denys, Florence Coussy, Camille Chakiba, Joana Mourato Ribeiro, Martine Piccart, Christine Desmedt, Michail Ignatiadis, Philippe Aftimos

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

Original language	English
Pages (from-to)	2381-2392
Number of pages	10
Journal	Future Oncology
Volume	18
Issue number	22
DOIs	https://doi.org/10.2217/fon-2022-0358
Publication status	Published - Jul 2022

Bibliographical note

Funding Information:
This study is supported by F. Hoffmann-La Roche Ltd. E Agostinetto: consultancy fees/honoraria from Eli Lilly and Sandoz; support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics and Istituto Gentili (all outside the submitted work). G Nader-Marta: travel grants from Roche and Bayer (all outside the submitted work). L Buisseret: postdoctoral clinical mandate (2020–2025) from the not-for-profit organization Foundation contre le Cancer (Brussels, Belgium); clinical research grant to the Institute: Astra Zeneca; institutional travel expenses: Roche; consultant: iTEOS therapeutics; speaker fee: BMS. D Taylor: consulting: Roche, Novartis, Daiichi Sankyo and Lilly; travel grants: Pfizer, Roche and AstraZeneca. C Fontaine: travel grants from Eli Lilly, Roche, Gilead, PharmaMar and Merck; advisory board paid by Eli Lilly and GSK to the oncology department

Funding Information:
G Nader-Marta: travel grants from Roche and Bayer (all outside the submitted work). L Buisseret: postdoctoral clinical mandate (2020–2025) from the not-for-profit organization Foundation contre le Cancer (Brussels, Belgium); clinical research grant to the Institute: Astra Zeneca; institutional travel expenses: Roche; consultant: iTEOS therapeutics; speaker fee: BMS. D Taylor: consulting: Roche, Novartis, Daiichi Sankyo and Lilly; travel grants: Pfizer, Roche and AstraZeneca. C Fontaine: travel grants from Eli Lilly, Roche, Gilead, PharmaMar and Merck; advisory board paid by Eli Lilly and GSK to the oncology department. FP Duhoux: received a postdoctoral clinical mandate (2017–034) from the not-for-profit organization Foundation Against Cancer (Brussels, Belgium); advisory/consultancy roles for Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Novartis, Pfizer, Pierre Fabre, Roche and Teva (paid to institution, outside the submitted work); speaker fees for Eli Lilly, Mundi Pharma, Novartis, Pfizer and Roche (paid to institution, outside the submitted work); travel support from Amgen, Pfizer, Roche and Teva. H Denys: consulting (paid to institution): Pfizer, Roche, AstraZeneca, Eli Lilly, Novartis, Amgen, Tesaro and GSK; travel support: Pfizer, Roche, PharmaMar, Teva and AstraZeneca. F Coussy: travel grants: Roche, Lilly and Novartis; research funding to institution: Novartis. C Chakiba: travel grants from Gilead and Pfizer. M Piccart: board member (scientific board): Oncolytics, Radius; consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Oncolytics, Periphagen, Pfizer, Roche, Seattle Genetics; Research grants to her Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon. M Ignatiadis: Consultant or advisory role (honoraria): Celgene, Novartis, Pfizer, Seattle Genetics and Tesaro; research grants to institute: Roche, Natera Inc and Pfizer. P Aftimos: consulting: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius and Deloitte; honoraria: Synthon, Amgen, Novartis and Gilead; travel grants: Amgen, MSD, Pfizer and Roche; research funding to institution: Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Funding Information:
This study is supported by F. Hoffmann-La Roche Ltd. E Agostinetto: consultancy fees/honoraria from Eli Lilly and Sandoz; support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics and Istituto Gentili (all outside the submitted work).

Publisher Copyright:
© 2022 Future Medicine Ltd.

Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.

Keywords

Breast Neoplasms/drug therapy
Cadherins
Carcinoma, Ductal, Breast/pathology
Carcinoma, Lobular/drug therapy
Clinical Trials, Phase II as Topic
Female
Humans
Neoadjuvant Therapy
Protein-Tyrosine Kinases/therapeutic use
Proto-Oncogene Proteins
Receptor, ErbB-2/genetics

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Agostinetto, E., Nader-Marta, G., Paesmans, M., Ameye, L., Veys, I., Buisseret, L., Neven, P., Taylor, D., Fontaine, C., Duhoux, F. P., Canon, J.-L., Denys, H., Coussy, F., Chakiba, C., Ribeiro, J. M., Piccart, M., Desmedt, C., Ignatiadis, M., & Aftimos, P. (2022). ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast. Future Oncology, 18(22), 2381-2392. https://doi.org/10.2217/fon-2022-0358

@article{cedca2ce68ae4c41a5db3e873bd65235,

title = "ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast",

abstract = "Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.",

keywords = "Breast Neoplasms/drug therapy, Cadherins, Carcinoma, Ductal, Breast/pathology, Carcinoma, Lobular/drug therapy, Clinical Trials, Phase II as Topic, Female, Humans, Neoadjuvant Therapy, Protein-Tyrosine Kinases/therapeutic use, Proto-Oncogene Proteins, Receptor, ErbB-2/genetics",

author = "Elisa Agostinetto and Guilherme Nader-Marta and Marianne Paesmans and Lieveke Ameye and Isabelle Veys and Laurence Buisseret and Patrick Neven and Donatienne Taylor and Christel Fontaine and Duhoux, {Francois P} and Jean-Luc Canon and Hannelore Denys and Florence Coussy and Camille Chakiba and Ribeiro, {Joana Mourato} and Martine Piccart and Christine Desmedt and Michail Ignatiadis and Philippe Aftimos",

note = "Funding Information: This study is supported by F. Hoffmann-La Roche Ltd. E Agostinetto: consultancy fees/honoraria from Eli Lilly and Sandoz; support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics and Istituto Gentili (all outside the submitted work). G Nader-Marta: travel grants from Roche and Bayer (all outside the submitted work). L Buisseret: postdoctoral clinical mandate (2020–2025) from the not-for-profit organization Foundation contre le Cancer (Brussels, Belgium); clinical research grant to the Institute: Astra Zeneca; institutional travel expenses: Roche; consultant: iTEOS therapeutics; speaker fee: BMS. D Taylor: consulting: Roche, Novartis, Daiichi Sankyo and Lilly; travel grants: Pfizer, Roche and AstraZeneca. C Fontaine: travel grants from Eli Lilly, Roche, Gilead, PharmaMar and Merck; advisory board paid by Eli Lilly and GSK to the oncology department Funding Information: G Nader-Marta: travel grants from Roche and Bayer (all outside the submitted work). L Buisseret: postdoctoral clinical mandate (2020–2025) from the not-for-profit organization Foundation contre le Cancer (Brussels, Belgium); clinical research grant to the Institute: Astra Zeneca; institutional travel expenses: Roche; consultant: iTEOS therapeutics; speaker fee: BMS. D Taylor: consulting: Roche, Novartis, Daiichi Sankyo and Lilly; travel grants: Pfizer, Roche and AstraZeneca. C Fontaine: travel grants from Eli Lilly, Roche, Gilead, PharmaMar and Merck; advisory board paid by Eli Lilly and GSK to the oncology department. FP Duhoux: received a postdoctoral clinical mandate (2017–034) from the not-for-profit organization Foundation Against Cancer (Brussels, Belgium); advisory/consultancy roles for Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Novartis, Pfizer, Pierre Fabre, Roche and Teva (paid to institution, outside the submitted work); speaker fees for Eli Lilly, Mundi Pharma, Novartis, Pfizer and Roche (paid to institution, outside the submitted work); travel support from Amgen, Pfizer, Roche and Teva. H Denys: consulting (paid to institution): Pfizer, Roche, AstraZeneca, Eli Lilly, Novartis, Amgen, Tesaro and GSK; travel support: Pfizer, Roche, PharmaMar, Teva and AstraZeneca. F Coussy: travel grants: Roche, Lilly and Novartis; research funding to institution: Novartis. C Chakiba: travel grants from Gilead and Pfizer. M Piccart: board member (scientific board): Oncolytics, Radius; consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Oncolytics, Periphagen, Pfizer, Roche, Seattle Genetics; Research grants to her Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon. M Ignatiadis: Consultant or advisory role (honoraria): Celgene, Novartis, Pfizer, Seattle Genetics and Tesaro; research grants to institute: Roche, Natera Inc and Pfizer. P Aftimos: consulting: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius and Deloitte; honoraria: Synthon, Amgen, Novartis and Gilead; travel grants: Amgen, MSD, Pfizer and Roche; research funding to institution: Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Funding Information: This study is supported by F. Hoffmann-La Roche Ltd. E Agostinetto: consultancy fees/honoraria from Eli Lilly and Sandoz; support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics and Istituto Gentili (all outside the submitted work). Publisher Copyright: {\textcopyright} 2022 Future Medicine Ltd. Copyright: Copyright 2022 Elsevier B.V., All rights reserved.",

year = "2022",

month = jul,

doi = "10.2217/fon-2022-0358",

language = "English",

volume = "18",

pages = "2381--2392",

journal = "Future Oncology",

issn = "1479-6694",

publisher = "Future Medicine Ltd.",

number = "22",

}

Agostinetto, E, Nader-Marta, G, Paesmans, M, Ameye, L, Veys, I, Buisseret, L, Neven, P, Taylor, D, Fontaine, C, Duhoux, FP, Canon, J-L, Denys, H, Coussy, F, Chakiba, C, Ribeiro, JM, Piccart, M, Desmedt, C, Ignatiadis, M & Aftimos, P 2022, 'ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast', Future Oncology, vol. 18, no. 22, pp. 2381-2392. https://doi.org/10.2217/fon-2022-0358

TY - JOUR

T1 - ROSALINE

T2 - a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast

AU - Agostinetto, Elisa

AU - Nader-Marta, Guilherme

AU - Paesmans, Marianne

AU - Ameye, Lieveke

AU - Veys, Isabelle

AU - Buisseret, Laurence

AU - Neven, Patrick

AU - Taylor, Donatienne

AU - Fontaine, Christel

AU - Duhoux, Francois P

AU - Canon, Jean-Luc

AU - Denys, Hannelore

AU - Coussy, Florence

AU - Chakiba, Camille

AU - Ribeiro, Joana Mourato

AU - Piccart, Martine

AU - Desmedt, Christine

AU - Ignatiadis, Michail

AU - Aftimos, Philippe

N1 - Funding Information: This study is supported by F. Hoffmann-La Roche Ltd. E Agostinetto: consultancy fees/honoraria from Eli Lilly and Sandoz; support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics and Istituto Gentili (all outside the submitted work). G Nader-Marta: travel grants from Roche and Bayer (all outside the submitted work). L Buisseret: postdoctoral clinical mandate (2020–2025) from the not-for-profit organization Foundation contre le Cancer (Brussels, Belgium); clinical research grant to the Institute: Astra Zeneca; institutional travel expenses: Roche; consultant: iTEOS therapeutics; speaker fee: BMS. D Taylor: consulting: Roche, Novartis, Daiichi Sankyo and Lilly; travel grants: Pfizer, Roche and AstraZeneca. C Fontaine: travel grants from Eli Lilly, Roche, Gilead, PharmaMar and Merck; advisory board paid by Eli Lilly and GSK to the oncology department Funding Information: G Nader-Marta: travel grants from Roche and Bayer (all outside the submitted work). L Buisseret: postdoctoral clinical mandate (2020–2025) from the not-for-profit organization Foundation contre le Cancer (Brussels, Belgium); clinical research grant to the Institute: Astra Zeneca; institutional travel expenses: Roche; consultant: iTEOS therapeutics; speaker fee: BMS. D Taylor: consulting: Roche, Novartis, Daiichi Sankyo and Lilly; travel grants: Pfizer, Roche and AstraZeneca. C Fontaine: travel grants from Eli Lilly, Roche, Gilead, PharmaMar and Merck; advisory board paid by Eli Lilly and GSK to the oncology department. FP Duhoux: received a postdoctoral clinical mandate (2017–034) from the not-for-profit organization Foundation Against Cancer (Brussels, Belgium); advisory/consultancy roles for Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Novartis, Pfizer, Pierre Fabre, Roche and Teva (paid to institution, outside the submitted work); speaker fees for Eli Lilly, Mundi Pharma, Novartis, Pfizer and Roche (paid to institution, outside the submitted work); travel support from Amgen, Pfizer, Roche and Teva. H Denys: consulting (paid to institution): Pfizer, Roche, AstraZeneca, Eli Lilly, Novartis, Amgen, Tesaro and GSK; travel support: Pfizer, Roche, PharmaMar, Teva and AstraZeneca. F Coussy: travel grants: Roche, Lilly and Novartis; research funding to institution: Novartis. C Chakiba: travel grants from Gilead and Pfizer. M Piccart: board member (scientific board): Oncolytics, Radius; consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Oncolytics, Periphagen, Pfizer, Roche, Seattle Genetics; Research grants to her Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon. M Ignatiadis: Consultant or advisory role (honoraria): Celgene, Novartis, Pfizer, Seattle Genetics and Tesaro; research grants to institute: Roche, Natera Inc and Pfizer. P Aftimos: consulting: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius and Deloitte; honoraria: Synthon, Amgen, Novartis and Gilead; travel grants: Amgen, MSD, Pfizer and Roche; research funding to institution: Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Funding Information: This study is supported by F. Hoffmann-La Roche Ltd. E Agostinetto: consultancy fees/honoraria from Eli Lilly and Sandoz; support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics and Istituto Gentili (all outside the submitted work). Publisher Copyright: © 2022 Future Medicine Ltd. Copyright: Copyright 2022 Elsevier B.V., All rights reserved.

PY - 2022/7

Y1 - 2022/7

N2 - Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

AB - Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

KW - Breast Neoplasms/drug therapy

KW - Cadherins

KW - Carcinoma, Ductal, Breast/pathology

KW - Carcinoma, Lobular/drug therapy

KW - Clinical Trials, Phase II as Topic

KW - Female

KW - Humans

KW - Neoadjuvant Therapy

KW - Protein-Tyrosine Kinases/therapeutic use

KW - Proto-Oncogene Proteins

KW - Receptor, ErbB-2/genetics

UR - http://www.scopus.com/inward/record.url?scp=85133750264&partnerID=8YFLogxK

U2 - 10.2217/fon-2022-0358

DO - 10.2217/fon-2022-0358

M3 - Article

C2 - 35695563

SN - 1479-6694

VL - 18

SP - 2381

EP - 2392

JO - Future Oncology

JF - Future Oncology

IS - 22

ER -

ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast

Abstract

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