Eribulin Yields Similar Benefit to Standard Chemotherapeutics for HER2-low and HER2-0 Metastatic Breast Cancer

Treatment with eribulin mesylate (Halaven) resulted in a trend towards improved overall survival (OS) in a population of patients diagnosed with HER2-low or HER2-0 metastatic breast cancer who received at least 1 prior chemotherapy agent vs other selections of standard physician's choice chemotherapy, according to an analysis presented at the 2022 San Antonio Breast Cancer Symposium (SABCS).

The analysis included patients treated in phase 3 Study 305 (NCT00388726)² and phase 3 Study 301 (NCT00337103)³, which compared eribulin with other chemotherapeutic controls in first and later lines in metastatic breast cancer.¹ The OS and progression-free survival (PFS) analysis for HER2-low disease included 235 patients treated with eribulin and 192 patients with control. The HER2-0 population included 470 patients treated with eribulin and 354 treated with control.

A trend toward longer median OS with eribulin vs control was observed in both the HER2-low subgroup (15.1 vs 12.0 months; HR, 0.88; 95% CI, 0.70-1.12) and in the HER2-0 subgroup (15.2 vs 12.5 months; HR, 0.78; 95% CI, 0.66-0.92).¹

The median PFS by independent imaging review was also longer with eribulin compared with the controls in the HER2-low cohort (4.0 vs 3.1 months; HR, 0.88; 95% CI, 0.68-1.14) and the HER2-0 cohort (3.9 vs 3.1 months; HR, 0.93; 95% CI, 0.78-1.11).¹

Although previous studies have suggested a difference in therapeutic outcomes with eribulin by HER2 status (low vs 0) in this setting, “the bottom line is that we didn’t see any meaningful difference,” Peter A. Kaufman, MD, professor of medicine in the Division of Hematology/Oncology at the University of Vermont Cancer Center in Burlington, said.

HER2-low has been defined by an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification or excess HER2 gene copy number, as measured by in situ hybridization. By this definition, approximately half of patients with breast cancer overall have HER2-low disease.

In the open-label study 305, patients were randomly assigned to either eribulin or treatment of physician’s choice (any single-agent chemotherapy or hormonal or biologic treatment approved for the treatment of cancer) after 2 to 5 prior chemotherapies, including anthracycline and a taxane.2 In study 301, patients were randomly assigned open label to eribulin or capecitabine following no more than 3 prior chemotherapies (no more than 2 for advanced disease), including an anthracycline and a taxane.³

Baseline characteristics were similar between eribulin and its comparators in both studies, in both the HER2-low and HER2-0 populations. Approximately 25% of patients in study 305 and slightly more than one-third in study 301 had triple-negative breast cancer (TNBC). Overall, 427 patients were classified as HER2-low and 824 patients as HER2-0.1

The objective response rate (ORR) by independent review was higher with eribulin vs control in patients with HER2-low disease. Among 226 evaluable patients treated with eribulin the ORR was 13.7% (95% CI, 9.5%-18.9%) vs 9.2% (95% CI, 5.5%-14.4%) among 184 patients treated with control. The rate of progressive disease was 29.6% vs 33.2%, respectively.¹

A similar trend was observed among patients with HER2-0 status. The ORR for the 450 evaluable patients who received eribulin was 10.2% (95% CI, 7.6%-13.4%) compared with 7.4% (95% CI, 4.9%-10.8%) for the 336 patients who received comparative chemotherapy. The rate of progressive disease was 30.7% vs 33.9%, respectively.¹

In a separate analysis of patients with TNBC in study 301, the median OS was longer with eribulin vs capecitabine in patients with HER2-low status (15.4 vs 10.3 months; HR, 0.57; 95% CI, 0.36-0.91) and those with HER2-0 status (14.4 vs 8.9 months; HR, 0.75; 95% CI, 0.55-1.02). “These findings are consistent with the robust efficacy of eribulin in patients with TNBC seen in other post hoc analyses,” Kaufman said.

In study 305, the median OS for patients with HER2-low disease who received eribulin vs chemotherapy was 7.4 months vs 7.7 months (HR, 1.34; 0.54-3.29). However, for those with HER2-0 status the median OS was 12.3 months vs 7.3 months (HR, 0.62; 95% CI, 0.33-1.14).

The median PFS was similar among patients with HER2-low and HER2-0 TNBC in both studies.

In terms of ORR, in study 305 among 28 patients with HER2-low disease who received eribulin only 1 patient responded (3.6%) and 15 (53.6%) had progressive disease. In the chemotherapy comparator arm (n = 14), 1 patient had a response (7.1%) and 9 (64.3%) had progressive disease. In the HER2-0 population, 2 patients had a response in the eribulin arm (n = 49) and 1 patient had a response in the comparator arm (n = 22).

In study 301, 42 patients with HER2-low TNBC received eribulin and 49 received capecitabine. The ORR was 9.5% vs 2%, respectively, with 21.4% and 38.8% of patients experiencing progressive disease. For those with HER2-0 disease, the ORR was 10.4% among 106 patients who received eribulin vs 8.6% among 81 patients who received capecitabine. The rate of progressive disease was 29.2% vs 38.3%, respectively.

HER2 testing in each study was locally performed, and the findings may be influenced the sensitivity of these assays to detect HER2 protein expression, Kaufman said. “There’s a broad dynamic range of HER2 and the IHC assay itself is not able to capture these lower levels of HER2 expression,” he said. “So, there could very well be some differences [in efficacy of eribulin] that we just are not able to tease out from a large study like this where we're incorporating local HER2 testing, for one, and then an assay that’s not the best assay by any means.”

References

1. Twelves C, Kaufman P, Im SA, et al. Efficacy of eribulin mesylate inHER2-low or HER2-0 metastatic breast cancer (MBC): results from an analysis of two phase III studies. Presented at 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX.
2. Cortes J, O’Shaughnessy J, Loesch D et al; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377(9769):914-923. doi:10.1016/S0140-6736(11)60070-6
3. Kaufman PA, Awada A, Twelves C et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015;33(6):594-601. doi:10.1200/JCO.2013.52.4892