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

Autor: Rugo HS; UCSF Helen, Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, San Francisco, CA, 94115, USA. Hope.Rugo@ucsf.edu., Trédan O; Centre Léon Bérard, Lyon, France., Ro J; National Cancer Center, Goyang, Republic of Korea., Morales SM; H. de Lleida Arnau de Vilanova, Lerida, Spain., Campone M; Institut de Cancérologie de l'Ouest, St Herblain-Nantes, France., Musolino A; University Hospital of Parma, Parma, Italy., Afonso N; Instituto Português de Oncologia Francisco Gentil, Porto, Portugal., Ferreira M; Instituto Português de Oncologia Francisco Gentil, Porto, Portugal., Park KH; Korea University Medical Center, Seoul, Republic of Korea., Cortes J; Ramón y Cajal University Hospital, Madrid and Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain., Tan AR; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.; Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA., Blum JL; Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, USA., Eaton L; Merck& Co., Inc., Kenilworth, NJ, USA., Gause CK; Merck& Co., Inc., Kenilworth, NJ, USA., Wang Z; Merck& Co., Inc., Kenilworth, NJ, USA., Im E; Merck& Co., Inc., Kenilworth, NJ, USA., Mauro DJ; Merck& Co., Inc., Kenilworth, NJ, USA., Jones MB; Merck& Co., Inc., Kenilworth, NJ, USA.; Checkmate Pharmaceuticals, Cambridge, MA, USA., Denker A; Merck& Co., Inc., Kenilworth, NJ, USA.; Alexion Pharmaceuticals, New Haven, CT, USA., Baselga J; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2017 Oct; Vol. 165 (3), pp. 601-609. Date of Electronic Publication: 2017 Jul 05.
DOI: 10.1007/s10549-017-4375-5
Abstrakt: 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.
Databáze: MEDLINE
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