Eribulin Plus Pembrolizumab in Patients With Metastatic Triple-Negative Breast Cancer (ENHANCE 1): A Phase 1b/2 Study.

Purpose As monotherapies, eribulin (chemotherapy) and pembrolizumab (immunotherapy) have shown promise for patients with metastatic triple-negative breast cancer (mTNBC). This phase 1b/2 study examined eribulin plus pembrolizumab as a potential mTNBC treatment in first-line and later-line settings. Experimental design In this open-label, single-arm, phase 1b/2 study, eligible patients had mTNBC, measurable disease, and {less than or equal to}2 prior systemic anticancer therapies in the metastatic setting. Patients were enrolled by number of prior systemic anticancer therapies (stratum 1: 0 vs stratum 2: 1-2) in the metastatic setting and further analyzed by tumor PD-L1-expression status. All patients received intravenous eribulin 1.4 mg/m2 on day 1 and day 8, plus intravenous pembrolizumab 200 mg on day 1, of 21-day cycles. The primary objectives were the safety, tolerability, and objective response rate (ORR) of this combination. Results The study included 167 patients (phase 1b, n=7; phase 2, n=160). The most common treatment-emergent adverse events were fatigue (66%), nausea (58%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). ORRs were 25.8% (95% CI: 15.8-38.0) for stratum 1 (n=66) and 21.8% (95% CI: 14.2-31.1) for stratum 2 (n=101). Patients with PD-L1+ tumors (combined positive score {greater than or equal to}1) had numerically higher ORR than those with PD-L1- tumors, particularly in stratum 1 (stratum 1: 34.5% [95% CI: 17.9-54.3] vs 16.1% [95% CI: 5.5-33.7]; stratum 2, 24.4% [95% CI: 12.9-39.5] vs 18.2% [95% CI: 8.2-32.7]). Conclusions Eribulin plus pembrolizumab was generally well tolerated and showed promising antitumor activity in mTNBC. Efficacy outcomes appeared influenced by line of therapy and PD-L1 status.