Glembatumumab Vedotin Appears Active in Heavily Treated Advanced Glycoprotein NMB–Overexpressing Breast Cancer and Triple-Negative Disease
In the randomized phase II EMERGE study reported in the Journal of Clinical Oncology, Yardley et al found that the anti–glycoprotein NMB (gpNMB) antibody-drug conjugate glembatumumab vedotin may improve response rate over alternative chemotherapy in patients with advanced refractory breast cancer characterized by higher expression of gpNMB in tumor cells or with triple-negative disease.
Study Details
In the study, 124 patients with refractory disease expressing gpNMB in ≥ 5% of epithelial or stromal cells were stratified according to gpNMB expression in tumor epithelial cells or low vs high intensity in stromal cells and randomly assigned 2:1 to receive glembatumumab vedotin at 1.88 mg/kg via 90-minute infusion once every 3 weeks (n = 83) or investigator’s choice of chemotherapy (n = 41). Chemotherapy included eribulin (Halaven; n = 15), ixabepilone (Ixempra; n = 7), gemcitabine (n = 5), vinorelbine (n = 5), doxorubicin (n = 3), and albumin-bound paclitaxel (Abraxane) (n = 2).
Patients had received a median of four lines of prior systemic therapy for advanced or metastatic disease, and 98% had stage IV disease. The primary endpoint was to detect an objective response rate in the glembatumumab vedotin group between 10% and 22.5%, with preplanned investigation of activity by gpNMB distribution and intensity.
Response Rates
The objective response rate was 6% in the glembatumumab vedotin group vs 7% in the investigator-selected chemotherapy group, with no evidence of between-group difference in rates in the three defined strata. However, response rates among patients with gpNMB expression in ≥ 25% of tumor epithelial cells were 30% (7/23) in the glembatumumab vedotin group and 9% (1/11) in the investigator-selected chemotherapy group. Further, unplanned analysis showed response rates of 18% (5/28) vs 0% (0/11) in patients with triple-negative breast cancer and 40% (4/10) vs 0% (0/6) in gpNMB-overexpressing triple-negative disease.
Adverse Events
Treatment-related grade 3 or 4 adverse events occurred in 40% vs 36% of patients, with glembatumumab vedotin being associated with less hematologic toxicity (eg, grade 3 or 4 neutropenia in 22% vs 29%, leukopenia in 4% vs 15%) and more any-grade rash (47% vs 2%, grade 3 or 4 in 4% vs 0%), pruritus (21% vs 2%), neuropathy (23% vs 12%, grade 3 or 4 in 3% vs 2%), and alopecia (25% vs 15%). Treatment-related adverse events resulted in discontinuation of study treatment in 8% vs 5% of patients.
The investigators concluded: Glembatumumab vedotin is well tolerated in heavily pretreated patients with breast cancer. Although the primary endpoint in advanced gpNMB-expressing breast cancer was not met for all enrolled patients (median tumor gpNMB expression, 5%), activity may be enhanced in patients with gpNMB-overexpressing tumors and/or [triple-negative breast cancer]. A pivotal phase II trial (METRIC [Metastatic Triple-Negative Breast Cancer]) is underway.”
Linda T. Vahdat, MD, of Weill Cornell Medical College, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Celldex Therapeutics. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
