A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer

Hope S. Rugo, Olivier Trédan, Jungsil Ro, Serafin M. Morales, Mario Campone, Antonino Musolino, Noémia Afonso, Marta Ferreira, Kyong Hwa Park, Javier Cortes, Antoinette R. Tan, Joanne L. Blum, Lamar Eaton, Christine K. Gause, Zhen Wang, Ellie Im, David J. Mauro, Mary Beth Jones, Andrew Denker, José Baselga

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: To evaluate whether adding humanized monoclonal insulin growth factor-1 receptor (IGF-1R) antibody (dalotuzumab) to mammalian target of rapamycin (mTOR) inhibitor (ridaforolimus) plus aromatase inhibitor (exemestane) improves outcomes in patients with estrogen receptor (ER)-positive advanced/metastatic breast cancer. Methods: This randomized, open-label, phase II trial enrolled 80 postmenopausal women with high-proliferation (Ki67 index staining ≥15%), ER-positive breast cancer that progressed after a non-steroidal aromatase inhibitor (NCT01605396). Randomly assigned patients were given oral ridaforolimus 10 mg QD 5 ×/week, intravenous dalotuzumab 10 mg/kg/week, and oral exemestane 25 mg/day (R/D/E, n = 40), or ridaforolimus 30 mg QD 5 ×/week and exemestane 25 mg/day (R/E; n = 40). Primary end point was progression-free survival (PFS). Results: Median PFS was 23.3 weeks for R/D/E versus 31.9 weeks for R/E (hazard ratio 1.18; 80% CI 0.81–1.72; P = 0.565). Grade 3–5 adverse events were reported in 67.5% of patients in the R/E arm and 59.0% in the R/D/E arm. Stomatitis (95.0 vs. 76.9%; P = 0.021) and pneumonitis (22.5 vs. 5.1%; P = 0.027) occurred more frequently in the R/E than the R/D/E arm; hyperglycemia (27.5 vs. 28.2%) occurred at a similar rate. Conclusions: R/D/E did not improve PFS compared with R/E. Because the PFS reported for R/E was similar to that reported for everolimus plus exemestane in patients with advanced breast cancer, it is possible that lower-dose ridaforolimus in the R/D/E arm (from overlapping toxicities with IGF1R inhibitor) contributed to lack of improved PFS.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalBreast Cancer Research and Treatment
DOIs
Publication statusAccepted/In press - 2017 Jul 5

Fingerprint

exemestane
Disease-Free Survival
Breast Neoplasms
Aromatase Inhibitors
Estrogen Receptors
Stomatitis
Growth Factor Receptors
Sirolimus
Hyperglycemia
Pneumonia
dalotuzumab
ridaforolimus
Insulin
Staining and Labeling

Keywords

  • Breast cancer
  • Dalotuzumab
  • Exemestane
  • IGF1R
  • mTOR
  • Ridaforolimus

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer. / Rugo, Hope S.; Trédan, Olivier; Ro, Jungsil; Morales, Serafin M.; Campone, Mario; Musolino, Antonino; Afonso, Noémia; Ferreira, Marta; Park, Kyong Hwa; Cortes, Javier; Tan, Antoinette R.; Blum, Joanne L.; Eaton, Lamar; Gause, Christine K.; Wang, Zhen; Im, Ellie; Mauro, David J.; Jones, Mary Beth; Denker, Andrew; Baselga, José.

In: Breast Cancer Research and Treatment, 05.07.2017, p. 1-9.

Research output: Contribution to journalArticle

Rugo, HS, Trédan, O, Ro, J, Morales, SM, Campone, M, Musolino, A, Afonso, N, Ferreira, M, Park, KH, Cortes, J, Tan, AR, Blum, JL, Eaton, L, Gause, CK, Wang, Z, Im, E, Mauro, DJ, Jones, MB, Denker, A & Baselga, J 2017, 'A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer', Breast Cancer Research and Treatment, pp. 1-9. https://doi.org/10.1007/s10549-017-4375-5
Rugo, Hope S. ; Trédan, Olivier ; Ro, Jungsil ; Morales, Serafin M. ; Campone, Mario ; Musolino, Antonino ; Afonso, Noémia ; Ferreira, Marta ; Park, Kyong Hwa ; Cortes, Javier ; Tan, Antoinette R. ; Blum, Joanne L. ; Eaton, Lamar ; Gause, Christine K. ; Wang, Zhen ; Im, Ellie ; Mauro, David J. ; Jones, Mary Beth ; Denker, Andrew ; Baselga, José. / A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer. In: Breast Cancer Research and Treatment. 2017 ; pp. 1-9.
@article{54797c36d0244ae08e835ce09d4cb073,
title = "A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer",
abstract = "Purpose: To evaluate whether adding humanized monoclonal insulin growth factor-1 receptor (IGF-1R) antibody (dalotuzumab) to mammalian target of rapamycin (mTOR) inhibitor (ridaforolimus) plus aromatase inhibitor (exemestane) improves outcomes in patients with estrogen receptor (ER)-positive advanced/metastatic breast cancer. Methods: This randomized, open-label, phase II trial enrolled 80 postmenopausal women with high-proliferation (Ki67 index staining ≥15{\%}), ER-positive breast cancer that progressed after a non-steroidal aromatase inhibitor (NCT01605396). Randomly assigned patients were given oral ridaforolimus 10 mg QD 5 ×/week, intravenous dalotuzumab 10 mg/kg/week, and oral exemestane 25 mg/day (R/D/E, n = 40), or ridaforolimus 30 mg QD 5 ×/week and exemestane 25 mg/day (R/E; n = 40). Primary end point was progression-free survival (PFS). Results: Median PFS was 23.3 weeks for R/D/E versus 31.9 weeks for R/E (hazard ratio 1.18; 80{\%} CI 0.81–1.72; P = 0.565). Grade 3–5 adverse events were reported in 67.5{\%} of patients in the R/E arm and 59.0{\%} in the R/D/E arm. Stomatitis (95.0 vs. 76.9{\%}; P = 0.021) and pneumonitis (22.5 vs. 5.1{\%}; P = 0.027) occurred more frequently in the R/E than the R/D/E arm; hyperglycemia (27.5 vs. 28.2{\%}) occurred at a similar rate. Conclusions: R/D/E did not improve PFS compared with R/E. Because the PFS reported for R/E was similar to that reported for everolimus plus exemestane in patients with advanced breast cancer, it is possible that lower-dose ridaforolimus in the R/D/E arm (from overlapping toxicities with IGF1R inhibitor) contributed to lack of improved PFS.",
keywords = "Breast cancer, Dalotuzumab, Exemestane, IGF1R, mTOR, Ridaforolimus",
author = "Rugo, {Hope S.} and Olivier Tr{\'e}dan and Jungsil Ro and Morales, {Serafin M.} and Mario Campone and Antonino Musolino and No{\'e}mia Afonso and Marta Ferreira and Park, {Kyong Hwa} and Javier Cortes and Tan, {Antoinette R.} and Blum, {Joanne L.} and Lamar Eaton and Gause, {Christine K.} and Zhen Wang and Ellie Im and Mauro, {David J.} and Jones, {Mary Beth} and Andrew Denker and Jos{\'e} Baselga",
year = "2017",
month = "7",
day = "5",
doi = "10.1007/s10549-017-4375-5",
language = "English",
pages = "1--9",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",

}

TY - JOUR

T1 - A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer

AU - Rugo, Hope S.

AU - Trédan, Olivier

AU - Ro, Jungsil

AU - Morales, Serafin M.

AU - Campone, Mario

AU - Musolino, Antonino

AU - Afonso, Noémia

AU - Ferreira, Marta

AU - Park, Kyong Hwa

AU - Cortes, Javier

AU - Tan, Antoinette R.

AU - Blum, Joanne L.

AU - Eaton, Lamar

AU - Gause, Christine K.

AU - Wang, Zhen

AU - Im, Ellie

AU - Mauro, David J.

AU - Jones, Mary Beth

AU - Denker, Andrew

AU - Baselga, José

PY - 2017/7/5

Y1 - 2017/7/5

N2 - Purpose: To evaluate whether adding humanized monoclonal insulin growth factor-1 receptor (IGF-1R) antibody (dalotuzumab) to mammalian target of rapamycin (mTOR) inhibitor (ridaforolimus) plus aromatase inhibitor (exemestane) improves outcomes in patients with estrogen receptor (ER)-positive advanced/metastatic breast cancer. Methods: This randomized, open-label, phase II trial enrolled 80 postmenopausal women with high-proliferation (Ki67 index staining ≥15%), ER-positive breast cancer that progressed after a non-steroidal aromatase inhibitor (NCT01605396). Randomly assigned patients were given oral ridaforolimus 10 mg QD 5 ×/week, intravenous dalotuzumab 10 mg/kg/week, and oral exemestane 25 mg/day (R/D/E, n = 40), or ridaforolimus 30 mg QD 5 ×/week and exemestane 25 mg/day (R/E; n = 40). Primary end point was progression-free survival (PFS). Results: Median PFS was 23.3 weeks for R/D/E versus 31.9 weeks for R/E (hazard ratio 1.18; 80% CI 0.81–1.72; P = 0.565). Grade 3–5 adverse events were reported in 67.5% of patients in the R/E arm and 59.0% in the R/D/E arm. Stomatitis (95.0 vs. 76.9%; P = 0.021) and pneumonitis (22.5 vs. 5.1%; P = 0.027) occurred more frequently in the R/E than the R/D/E arm; hyperglycemia (27.5 vs. 28.2%) occurred at a similar rate. Conclusions: R/D/E did not improve PFS compared with R/E. Because the PFS reported for R/E was similar to that reported for everolimus plus exemestane in patients with advanced breast cancer, it is possible that lower-dose ridaforolimus in the R/D/E arm (from overlapping toxicities with IGF1R inhibitor) contributed to lack of improved PFS.

AB - Purpose: To evaluate whether adding humanized monoclonal insulin growth factor-1 receptor (IGF-1R) antibody (dalotuzumab) to mammalian target of rapamycin (mTOR) inhibitor (ridaforolimus) plus aromatase inhibitor (exemestane) improves outcomes in patients with estrogen receptor (ER)-positive advanced/metastatic breast cancer. Methods: This randomized, open-label, phase II trial enrolled 80 postmenopausal women with high-proliferation (Ki67 index staining ≥15%), ER-positive breast cancer that progressed after a non-steroidal aromatase inhibitor (NCT01605396). Randomly assigned patients were given oral ridaforolimus 10 mg QD 5 ×/week, intravenous dalotuzumab 10 mg/kg/week, and oral exemestane 25 mg/day (R/D/E, n = 40), or ridaforolimus 30 mg QD 5 ×/week and exemestane 25 mg/day (R/E; n = 40). Primary end point was progression-free survival (PFS). Results: Median PFS was 23.3 weeks for R/D/E versus 31.9 weeks for R/E (hazard ratio 1.18; 80% CI 0.81–1.72; P = 0.565). Grade 3–5 adverse events were reported in 67.5% of patients in the R/E arm and 59.0% in the R/D/E arm. Stomatitis (95.0 vs. 76.9%; P = 0.021) and pneumonitis (22.5 vs. 5.1%; P = 0.027) occurred more frequently in the R/E than the R/D/E arm; hyperglycemia (27.5 vs. 28.2%) occurred at a similar rate. Conclusions: R/D/E did not improve PFS compared with R/E. Because the PFS reported for R/E was similar to that reported for everolimus plus exemestane in patients with advanced breast cancer, it is possible that lower-dose ridaforolimus in the R/D/E arm (from overlapping toxicities with IGF1R inhibitor) contributed to lack of improved PFS.

KW - Breast cancer

KW - Dalotuzumab

KW - Exemestane

KW - IGF1R

KW - mTOR

KW - Ridaforolimus

UR - http://www.scopus.com/inward/record.url?scp=85021784217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021784217&partnerID=8YFLogxK

U2 - 10.1007/s10549-017-4375-5

DO - 10.1007/s10549-017-4375-5

M3 - Article

C2 - 28681171

AN - SCOPUS:85021784217

SP - 1

EP - 9

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

ER -