Absolute Lymphocyte Count May Predict Eribulin Benefit in Breast Cancer

Javier Cortes, MD

A high absolute lymphocyte count (ALC) at baseline appears to be an independent predictor for longer overall survival (OS) in patients with metastatic breast cancer who are treated with eribulin mesylate (Halaven), according to a poster presented at the 2019 San Antonio Breast Cancer Symposium.¹

In examining data from 2 phase III studies—EMBRACE and Study 301—patients with high baseline ALC values were found to experience greater eribulin benefit on OS versus patients with low baseline ALC across cutoff values from 1300 µL to 1750/µL, lead investigator Javier Cortes, MD, and colleagues reported.

In the multicenter open-label EMBRACE study, which enrolled women with locally recurrent or metastatic breast cancer who were randomized to eribulin or treatment of physician’s choice (TPC), patients with a baseline ALC ≥1500/µL who were randomized to eribulin had significantly longer OS than those randomized to TPC (median OS, 15.6 vs 11.4 months; HR, 0.586; 95% CI, 0.437-0.784; P <.001).

In the open-label Study 301, which randomized patients with advanced or metastatic breast cancer who had received prior anthracycline- and taxane-based therapy to eribulin or capecitabine. Among patients with baseline ALC ≥1500/µL, those in the eribulin arm of the study had significantly prolonged OS compared with those in the capecitabine arm (median OS, 19.6 vs 16.0 months; HR, 0.81; 95% CI, 0.662-0.993; P = .042).

“This hypothesis-generating study speculates that baseline ALC may be useful in the selection of patients to be treated with eribulin,” Cortes et al wrote.

Eribulin is a nontaxane synthetic inhibitor of microtubule dynamics approved for use in locally advanced or metastatic breast cancer after 2 previous lines of chemotherapy.

In EMBRACE, 762 women were enrolled and randomized to eribulin at 1.4 mg/m² intravenously on days 1 and 8 of a 21-day cycle or TPC. Median OS of the patients assigned to eribulin was significantly better than the TPC arm, although no significant difference was observed in progression-free survival by independent review.² There were 500 and 251 patients in the eribulin and TPC arms, respectively, who had an evaluable baseline ALC.

Study 301 enrolled 1102 women who were randomized to the same dosing schedule on eribulin as in Study 301 or capecitabine at 1.25 g/m² orally on days 1 to 14 of a 21-day cycle. The study did not meet its primary endpoint of an improvement in OS, but median OS was numerically longer in the eribulin arm versus the capecitabine arm (15.9 vs 14.5 months, respectively; P = .056).³ Of those enrolled, 553 in the eribulin arm and 547 in the capecitabine arm had an evaluable baseline ALC.

The posthoc analysis presented at SABCS assessed predictors for OS in patients treated with eribulin in the 2 phase III studies, focusing on ALC, a peripheral immune parameter.

In EMBRACE, baseline characteristics were similar between the eribulin and TPC groups and between the ALC cutoff groups, except for a higher percentage of patients with >2 organs involved in both treatment arms in the ALC <1500/ µL cohorts.

Whereas the median OS in EMBRACE was superior with eribulin among patients with baseline ALC ≥1500/µL, among those with ALC <1500/ µL at baseline, the median OS was 11.6 months in the eribulin arm versus 10.3 months in the TPC arm (HR, 1.002; 95% CI, 0.800-1.253).

“Patients in EMBRACE with high baseline ALC (≥1500/µL) experienced greater OS benefit following eribulin treatment versus patients with low baseline ALC (<1500/uL) across cutoff values from 1400/µL to 1700/µL (interaction P value <.05),” Cortes et al wrote.

In Study 301, baseline characteristics were similar between treatment arms and between the ALC cutoffs, except that there was a higher percentage of patients with hormone receptor—positive disease at baseline in both the ALC ≥1500/µL versus the ALC <1500/µL cohorts in both treatment arms.

The median OS with eribulin in Study 301 was 19.6 months in patients who had baseline ALC ≥1500/µL versus 14.6 months in those with baseline ALC <1500/ µL. Among the patients with ALC <1500/µL at baseline, the median OS was 14.6 versus 12.5 months in the eribulin and capecitabine arms, respectively (HR, 0.907; 95% CI, 0.758-1.084).

References

1. Cortes J, Perez-Garcia JM, Nomoto K, et al. Absolute lymphocyte count (ALC) is a predictor of eribulin benefit in advanced or metastatic breast cancer (MBC). Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14; San Antonio, TX. Abstract P4-10-08. doi: 10.1016/S0140-6736(11)60070-6.
2. Cortes J, O’Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377:914-923.
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;33:594-601. doi: 10.1200/JCO.2013.52.4892.