Eribulin–pembrolizumab combo shows potential against mTNBC

The combination of eribulin plus pembrolizumab is well tolerated and demonstrates favourable antitumour activity in metastatic triple-negative breast cancer (mTNBC), with line of therapy and PD-L1 status factoring in treatment efficacy, according to the results of the phase Ib/II ENHANCE 1 study.

ENHANCE 1 included 167 patients: seven in phase Ib and 160 in phase II. For each 21-day cycle, patients in phase Ib received intravenous (IV) eribulin 1.4 mg/m² on days 1 and 8, along with IV pembrolizumab 200 mg on day 1. The same dose would be used in the phase II treatment if only ≤1 patient had a dose-limiting toxicity (DLT) in the first cycle. However, if DLT occurred in ≥2 patients, then the eribulin dose would be reduced to 1.1 mg/m².

Patients in the phase II part of the study were enrolled into two strata defined by the number of prior systemic therapies in the metastatic setting (stratum 1: no prior treatment; stratum 2: 1–2 prior treatments).

The safety profile of eribulin plus pembrolizumab was consistent with that reported in monotherapy studies. Fatigue (66 percent) and nausea (58 percent) were the most common treatment-emergent adverse events, followed by peripheral sensory neuropathy (41 percent), alopecia (40 percent), and constipation (37 percent). TEAEs resulted in discontinuation of eribulin, pembrolizumab, or both in 6 percent, 9 percent, and 11 percent of patients, respectively.

The treatment combination yielded an objective response rate (ORR) of 25.8 percent (95 percent confidence interval [CI], 15.8–38.0) for stratum 1 (n=66) and 21.8 percent (95 percent CI, 14.2–31.1) for stratum 2 (n=101).

ORR among patients with PD-L1–positive tumours (combined positive score ≥1) was numerically higher than among those with negative PD-L1–negative status. This was especially evident in stratum 1 (34.5 percent vs 16.1 percent) than in stratum 2 (24.4 percent vs 18.2 percent).

The findings support further clinical development of the eribulin–pembrolizumab combination as a potential antitumour strategy for patients with mTNBC.