Breast Cancer Research and Treatment

, Volume 165, Issue 3, pp 601–609 | Cite as

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

  • Hope S. RugoEmail author
  • 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
Clinical trial



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.


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).


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.


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.


Breast cancer Ridaforolimus mTOR Dalotuzumab IGF1R Exemestane 



We thank the patients and their families for their participation and support during the study as well as the study center staff and principal investigators. Editorial support was provided by Tim Ibbotson, PhD, of ApotheCom and was funded by Merck & Co., Inc., Kenilworth, NJ.


This work was supported by a grant from Merck & Co., Inc.

Conflicts of interest

JC has received fees for lectures and consulting from Roche, Celgene, Novartis, and Eisai. HSR has received research support from Merck & Co., Inc. and Novartis. ART received grants from Merck & Co., Inc. for conducting this study. AD, CKG, EI, MBJ, DJM, and ZW are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ and may hold stock or stock options in the company. MF has received grants from Merck Sharp & Dohme Corp. and AstraZeneca, grants and non-financial support from Novartis, and F. Hoffmann-La Roche, and non-financial support from Merck Sharp & Dohme Corp. NA, JB, JLB, MC, LE, AM, JR, SMM, OT, and KHP have nothing to disclose.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Independent ethics committees reviewed and approved the protocol and applicable amendments for each institution.

Informed consent

Written informed consent was obtained from all participants.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Hope S. Rugo
    • 1
    Email author
  • Olivier Trédan
    • 2
  • Jungsil Ro
    • 3
  • Serafin M. Morales
    • 4
  • Mario Campone
    • 5
  • Antonino Musolino
    • 6
  • Noémia Afonso
    • 7
  • Marta Ferreira
    • 7
  • Kyong Hwa Park
    • 8
  • Javier Cortes
    • 9
  • Antoinette R. Tan
    • 10
    • 15
  • Joanne L. Blum
    • 11
  • Lamar Eaton
    • 12
  • Christine K. Gause
    • 12
  • Zhen Wang
    • 12
  • Ellie Im
    • 12
  • David J. Mauro
    • 12
  • Mary Beth Jones
    • 12
    • 16
  • Andrew Denker
    • 12
    • 13
  • José Baselga
    • 14
  1. 1.UCSF Helen, Diller Family Comprehensive Cancer CenterSan FranciscoUSA
  2. 2.Centre Léon BérardLyonFrance
  3. 3.National Cancer CenterGoyangRepublic of Korea
  4. 4.H. de Lleida Arnau de VilanovaLeridaSpain
  5. 5.Institut de Cancérologie de l’OuestSt Herblain-NantesFrance
  6. 6.University Hospital of ParmaParmaItaly
  7. 7.Instituto Português de Oncologia Francisco GentilPortoPortugal
  8. 8.Korea University Medical CenterSeoulRepublic of Korea
  9. 9.Ramón y Cajal University HospitalMadrid and Vall d´Hebron Institute of Oncology (VHIO)BarcelonaSpain
  10. 10.Rutgers Cancer Institute of New JerseyNew BrunswickUSA
  11. 11.Baylor Sammons Cancer CenterTexas Oncology, US OncologyDallasUSA
  12. 12.Merck& Co., Inc.KenilworthUSA
  13. 13.Alexion PharmaceuticalsNew HavenUSA
  14. 14.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  15. 15.Levine Cancer InstituteCarolinas HealthCare SystemCharlotteUSA
  16. 16.Checkmate PharmaceuticalsCambridgeUSA

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