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Hormone Receptor Status Is Not a Factor in the HER2CLIMB Study of Tucatinib Combination Treatment for Patients with HER2-Positive Metastatic Breast Cancer

Conference Correspondent 

Tucatinib (Tukysa) is a highly selective oral tyrosine kinase inhibitor of human epidermal growth factor receptor 2 (HER2) that minimally inhibits EGFR that recently received approval by the US Food and Drug Administration for the treatment of patients with HER2-positive metastatic breast cancer, including patients with brain metastases whose cancers have progressed on ≥1 previous anti-HER2 regimens in the metastatic setting.

Patients with HER2-positive metastatic breast cancer previously treated with trastuzumab (Herceptin), pertuzumab (Perjeta), and trastuzumab emtansine (Kadcyla) were randomized to receive tucatinib or placebo in combination with trastuzumab and capecitabine (Xeloda) in the HER2CLIMB pivotal trial published in the New England Journal of Medicine.1

Erika Hamilton, MD, Director, Breast Cancer and Gynecologic Cancer Research Program, Sarah Cannon Research Institute, Nashville, TN, and colleagues provided an exploratory analysis describing outcomes in the HER2CLIMB trial based on hormone receptor status.

In combination with trastuzumab and capecitabine, participants were randomized 2:1 to receive tucatinib or placebo. A baseline brain magnetic resonance imaging was acquired for all patients. Assignment to the hormone receptor–positive subgroup included all patients with HER2-positive metastatic breast cancer who were positive for either or both estrogen receptor and progesterone receptor (>1%). Assignment to the hormone receptor–negative subgroup included patients not meeting the above criteria.

Progression-free survival was evaluated in the first 480 patients enrolled for the exploratory hormone receptor–positive, hormone receptor–negative efficacy analysis. In patients with baseline brain metastases, progression-free survival, overall survival, and confirmed objective response rate in patients with measurable disease were assessed in the total study population.

In total, 612 patients were enrolled in the HER2CLIMB study, with 60% (N = 370) having hormone receptor–positive tumors and 40% (N = 242) having hormone receptor–negative tumors. There was a 42% reduction in the risk for progression or death in the tucatinib arm in the hormone receptor–positive group (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.42-0.80; P = .0008). Median (95% CI) progression-free survival was 7.6 months in the tucatinib arm compared with 5.6 months in the control arm. There was a 46% reduction in the risk for progression or death in the tucatinib arm in the hormone receptor–negative group (HR, 0.54; 95% CI, 0.34-0.86; P = .008). Median progression-free survival was 8.1 months in the tucatinib arm compared with 4.2 months in the control arm.

Median overall survival was 21.7 months in the total population compared with 18.2 months in hormone receptor–positive arm when comparing the tucatinib arm with the control arm. Median overall survival in hormone receptor–negative arm was 31.1 months in the tucatinib arm compared with 14.1 months in the control arm.

There was a 52% reduction in the risk for progression or death (HR, 0.48; 95% CI, 0.31-0.75; P = .0008) in patients with brain metastases in the hormone receptor–positive group (N = 166 [45%]). Median progression-free survival was 7.5 months in the tucatinib arm compared with 5.1 months in the control arm, and median overall survival was 18.1 months compared with 12.8 months, respectively.

There was a 50% reduction in the risk for progression or death (HR, 0.50; 95% CI, 0.27-0.95; P = .03) in patients with brain metastases in the hormone receptor–negative group (N = 125 [52%]). Median progression-free survival was 7.8 months (6.1-11.6 months) in the tucatinib arm compared with 5.4 months in the control arm, and median overall survival was 18.5 months compared with 11.5 months, respectively. Objective response rate in the total population was numerically higher in the tucatinib arm compared with the control arm regardless of hormone receptor status (hormone receptor–positive, 37.4% [95% CI, 30.8-44.5] compared with 27.1% [95% CI, 19.0-36.6], respectively, and hormone receptor–negative 45.3% [95% CI, 36.7-54.0] compared with 15.6% [95% CI, 7.8-26.9], respectively).

The investigators concluded that among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, the addition of tucatinib to trastuzumab and capecitabine showed clinically meaningful improvements of progression-free survival, overall survival, and confirmed objective response rate that was not dependent on hormone receptor status. Lastly and importantly, similar benefit from the addition of tucatinib to trastuzumab and capecitabine was obtained by patients with hormone receptor–positive and hormone receptor–negative metastatic breast cancer with brain metastases.

Source: Hamilton E, Reinisch M, Loi S, et al. Tucatinib vs placebo in combination with trastuzumab and capecitabine for patients with locally advanced unresectable or HER2-positive metastatic breast cancer (HER2CLIMB): Outcomes by hormone receptor status. Presented at: San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PD3-08.


Reference

  • Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. Erratum in: N Engl J Med. 2020;382:586.

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