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01-06-2017 | Clinical trial

A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer

Authors: José Baselga, Serafin M. Morales, Ahmad Awada, Joanne L. Blum, Antoinette R. Tan, Marianne Ewertz, Javier Cortes, Beverly Moy, Kathryn J. Ruddy, Tufia Haddad, Eva M. Ciruelos, Peter Vuylsteke, Scot Ebbinghaus, Ellie Im, Lamar Eaton, Kumudu Pathiraja, Christine Gause, David Mauro, Mary Beth Jones, Hope S. Rugo

Published in: Breast Cancer Research and Treatment | Issue 3/2017

Abstract

Purpose

Combining the mTOR inhibitor ridaforolimus and the anti-IGFR antibody dalotuzumab demonstrated antitumor activity, including partial responses, in estrogen receptor (ER)-positive advanced breast cancer, especially in high proliferation tumors (Ki67 > 15%).

Methods

This randomized, multicenter, international, phase II study enrolled postmenopausal women with advanced ER-positive breast cancer previously treated with a nonsteroidal aromatase inhibitor (NCT01234857). Patients were randomized to either oral ridaforolimus 30 mg daily for 5 of 7 days (once daily [qd] × 5 days/week) plus intravenous dalotuzumab 10 mg/kg/week or oral exemestane 25 mg/day, and stratified by Ki67 status. Due to a high incidence of stomatitis in the ridaforolimus–dalotuzumab group, two sequential, nonrandomized, reduced-dose cohorts were explored with ridaforolimus 20 and 10 mg qd × 5 days/week. The primary endpoint was progression-free survival (PFS).

Results

Median PFS was 21.4 weeks for ridaforolimus 30 mg qd × 5 days/week plus dalotuzumab 10 mg/kg (n = 29) and 24.3 weeks for exemestane (n = 33; hazard ratio = 1.00; P = 0.5). Overall survival and objective response rates were similar between treatment arms. The incidence of drug-related, nonserious, and serious adverse events was higher with ridaforolimus/dalotuzumab (any ridaforolimus dose) than with exemestane. Lowering the ridaforolimus dose reduced the incidence of grade 3 stomatitis, but overall toxicity remained higher than acceptable at all doses without improved efficacy.

Conclusions

The combination of ridaforolimus plus dalotuzumab was no more effective than exemestane in patients with advanced ER-positive breast cancer, and the incidence of adverse events was higher. Therefore, the combination is not being further pursued.

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Title: A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer
Authors: José Baselga
Serafin M. Morales
Ahmad Awada
Joanne L. Blum
Antoinette R. Tan
Marianne Ewertz
Javier Cortes
Beverly Moy
Kathryn J. Ruddy
Tufia Haddad
Eva M. Ciruelos
Peter Vuylsteke
Scot Ebbinghaus
Ellie Im
Lamar Eaton
Kumudu Pathiraja
Christine Gause
David Mauro
Mary Beth Jones
Hope S. Rugo
Publication date: 01-06-2017
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4199-3

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