Eribulin Proves Noninferior to Taxane as Combination Partner With Trastuzumab and Pertuzumab in HER2+ Breast Cancer

Trastuzumab (Herceptin) and pertuzumab (Perjeta) plus eribulin was noninferior to trastuzumab plus pertuzumab and a taxane in terms of progression-free survival (PFS) in patients with HER2-positive locally advanced or metastatic breast cancer, according to findings from the phase 3 EMERALD trial (NCT03264547) published in the Journal of Clinical Oncology. Additionally, the median time to quality of life (QOL) deterioration was numerically longer with the eribulin regimen vs the taxane regimen.

Findings from the study demonstrated that patients in the eribulin arm (n = 224) achieved a median PFS of 14.0 months (95% CI, 11.7-16.2) compared with 12.9 months (95% CI, 10.8-15.6) in the taxane group (n = 222; HR, 0.95; 95% CI, 0.76-1.19; log-rank P = .68). The objective response rate (ORR) was 76.8% in the eribulin arm vs 75.2% in the taxane group. The clinical benefit rates were 88.8% vs 86.9%, respectively.

“The upper limit of the 95% CI for HR did not exceed the prespecified noninferiority margin of 1.33, thus confirming the noninferiority of the study regimen to the control regimen,” the study authors wrote.

Additional findings showed that the median overall survival (OS) was 65.3 months in the taxane arm and was not yet reached in the eribulin arm (HR, 1.09; 95% CI, 0.76-1.58; log-rank P = .73). The median time to QOL deterioration was 7.16 months (95% CI, 6.28-8.31) vs 4.57 months (95% CI, 4.17-6.14) in patients included in the eribulin (n = 221) and taxane (n = 216) arm QOL analysis, respectively (HR, 0.80; 95% CI, 0.66-0.99; log-rank P = .08). Subgroup analyses for OS and PFS displayed no clear findings favoring either group.

In terms of safety, any-grade drug-related treatment-emergent adverse effects (AEs) of special interest occurred in 93.3% of patients in the eribulin arm and 96.3% of those in the taxane arm. Any-grade infusion reaction (24.8% vs 13.4%), skin-related AEs (62.4% vs 40.6%), diarrhea (54.1% vs 36.6%), and edema (42.2% vs 8.5%) were more common with taxane compared with eribulin, respectively. Any-grade neutropenia was higher in the eribulin arm (61.6%) vs the taxane arm (30.7%); however febrile neutropenia occurred less frequently in the eribulin group (4.9%) vs the taxane group (8.7%). Further, any-grade peripheral sensory neuropathy (61.2% vs 52.8%), peripheral motor neuropathy (5.4% vs 3.7%), and cardiac events (7.1% vs 6.0%) occurred more frequently in the eribulin arm vs taxane arm, respectively.

EMERALD was a multicenter, open-label study evaluating the noninferority of trastuzumab in combination with pertuzumab plus eribulin vs trastuzumab plus pertuzumab with docetaxel or paclitaxel in patients with HER2-positive locally advanced or metastatic breast cancer. Patients enrolled were 20 to 70 years of age, had not undergone prior cytotoxic chemotherapy besides trastuzumab emtansine (T-DM1; Kadcyla) for locally advanced or metastatic disease, had an ECOG performance status of 0 or 1, had a left ventricular ejection fraction of at least 50%, and had adequate organ function.

Patients were randomly assigned 1:1 to receive eribulin or a taxane, both in combination with trastuzumab at a loading dose of 8mg/kg and maintenance doses of 6 mg/kg and pertuzumab at a loading dose of 840 mg and maintenance doses of 420 mg; both were administered intravenously on day 1. Eribulin was administered at a dose of 1.4 mg/m2 once daily on days 1 and 8 and patients in the taxane arm received either docetaxel at a dose of 75 mg/m2 once on day 1 or paclitaxel at a dose of 80 mg/m2 once daily on days 1, 8, and 15. Treatment was administered in 21-day cycles, with a recommended minimum of 6 cycles, and continued until disease progression, unacceptable toxicity, or patient withdrawal.

The primary end point of the study was PFS per RECIST 1.1 criteria. Secondary end points included ORR, OS, QOL, and safety.

At baseline, the median age in the eribulin and taxane group was 56.0 years (range, 29.0-70.0) vs 57.0 years (range, 32.0-70.0), respectively. Most patients in both groups were postmenopausal (67.9% vs 76.6%), had an ECOG performance status of 0 (82.1% vs 84.2%), had estrogen receptor-positive disease (57.1% vs 58.1%), and had a HER2 immunohistochemistry status of 3+ (82.1% vs 76.1%). Patients in both arms received prior chemotherapy (35.3% vs 32.9%), including an anthracycline plus a taxane (25.4% vs 22.5%), a taxane only (6.3% vs 7.7%), an anthracycline only (2.7% vs 2.3%), or another form of chemotherapy (0.9% vs 0.5%), respectively.

“To our knowledge, the present study is the first phase 3 trial that showed the noninferiority of eribulin to taxane when used with the dual HER2 blockade as first-line systemic treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer,” the study authors wrote in conclusion. “Previous studies have provided evidence for the manageable safety profile of eribulin relative to that of other agents used to treat metastatic breast cancer. Considering the toxicity findings and favorable QOL outcomes of the present study, eribulin may be better tolerated than a taxane as a chemotherapeutic partner for trastuzumab plus pertuzumab. It may be a particularly valuable option for patients who have hypersensitivity to taxanes.”

Reference

1. Yamashita T, Saji S, Takano T, et al. Trastuzumab-pertuzumab plus eribulin or taxane as first-line chemotherapy for human epidermal growth factor 2–positive locally advanced/metastatic breast cancer: the randomized noninferiority phase III EMERALD trial. J Clin Oncol. Published online January 9, 2025. doi:10.1200/JCO-24-01888