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

作者：Rugo Hope S^*; Tredan Olivier; Ro Jungsil; Morales Serafin M; Campone Mario; Musolino Antonino; Afonso Noemia; 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 Jose

来源：Breast Cancer Research and Treatment, 2017, 165(3): 601-609.

DOI：10.1007/s10549-017-4375-5

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

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 ae<yen>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 x/week, intravenous dalotuzumab 10 mg/kg/week, and oral exemestane 25 mg/day (R/D/E, n = 40), or ridaforolimus 30 mg QD 5 x/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.

• 出版日期2017-10