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Trastuzumab and Chemotherapy Prolong Survival in Patients With Breast Cancer and CNS Metastases

Jason M. Broderick @jasoncology
Published: Monday, Jul 18, 2011

trastuzumab (Herceptin)Treatment with either trastuzumab (Herceptin), chemotherapy, or surgery extended the lives of patients with HER2-positive metastatic breast cancer (MBC) following a diagnosis of central nervous system (CNS) metastases, according to data from the registHER study.

The prospective, observational study involved 1023 patients with newly diagnosed HER2-positive metastatic breast cancer, 1012 of whom had confirmed HER2-positive tumors. Three hundred seventy-seven patients in the study had CNS metastases. Of these 377 patients, 68.4% (n = 258) received trastuzumab after diagnosis, 69.5% (n = 262) received chemotherapy, 71.4% (n = 269) received radiation therapy, and 7.7% (n = 29) had surgery.

After a CNS disease diagnosis, median overall survival (OS) in MBC patients receiving treatment versus control (ie, no treatment) increased by 13.7 months with trastuzumab (17.5 vs 3.8 mo; hazard ratio [HR] = 0.25; 95% confidence interval [CI], 0.20-0.33; P <.001), 12.7 months with chemotherapy (16.4 vs 3.7 mo; HR = 0.62; 95% CI, 0.47-0.82; P <.001), and 9 months with surgery (20.3 vs 11.3 mo; HR = 0.55; 95% CI, 0.34-0.88; P = .013). While treatment with radiotherapy also appeared to prolong OS (13.9 vs 8.4 mo), the result was not significant (P = .134).

Adam Brufsky, MD, PhD

Adam Brufsky, MD, PhD

Multivariable proportional hazards analyses confirmed the efficacy of trastuzumab and chemotherapy (HR =0.33, P <.001; HR = 0.64, P = .002, respectively). In the same analysis, however, outcomes with surgery and radiotherapy failed to achieve statistical significance (P = .062 and P = .898, respectively).

In describing how the results translate to clinical practice, lead researcher Adam Brufsky, MD, PhD, professor of medicine and associate director of clinical investigation at the University of Pittsburgh Cancer Institute, told he would now recommend “[continuing] Herceptin and chemo…if someone had brain metastases.” Brufsky had previously thought the treatments would be ineffective in this setting.

Cancer spreads to the CNS in 10% to 16% of women with late-stage breast cancer, according to Brufsky and colleagues. “As the largest prospectively followed cohort of patients with HER2-positive MBC, registHER afford[ed] a unique opportunity to study…CNS metastases in this patient population in the context of contemporary therapies,” the authors wrote.

Asked about other ongoing research in treating CNS metastases in patients with breast cancer, Brufsky said, “A lot revolves around trying to find biomarkers that predict for brain mets, as well as trying to find drugs that cross the blood—brain barrier such as Tykerb [lapatinib] and Xeloda [capecitabine].”

Brufsky AM, Mayer M, Rugo HS, et al. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011;17(14):4834-4843.

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