Bevacizumab plus second-line chemotherapy extended PFS in HER-2–negative breast cancer

The addition of bevacizumab to second-line chemotherapy significantly extended PFS among patients with locally recurrent or metastatic HER-2–negative breast cancer whose disease progressed after previous treatment with the same combination, according to results of a randomized phase 3 trial presented at the European Society for Medical Oncology Annual Congress in Madrid.

The open-label TANIA trial included 494 patients with HER-2–negative, locally recurrent or metastatic breast cancer. All patients underwent ≥12 weeks of first-line treatment with bevacizumab (Avastin, Genentech) plus chemotherapy but subsequently experienced disease progression.

Gunter von Minckwitz, MD, PhD, managing director of the German Breast Group Research Institute, and colleagues randomly assigned half of the patients to receive second-line chemotherapy plus bevacizumab (either 15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks). The other patients received chemotherapy alone.

Gunter von Minckwitz

Baseline characteristics — including median age (56 years vs. 54 years), percentage of those with triple-negative disease (19.8% vs. 23.1%) and percentage of those with disease-free interval ≥12 months (7.3% vs. 9.7%) — were similar between those assigned bevacizumab plus chemotherapy and those assigned chemotherapy alone.

Second-line therapy continued until disease progression, unacceptable toxicity or withdrawal.

At progression, patients assigned chemotherapy alone received third-line chemotherapy without bevacizumab, whereas those assigned bevacizumab plus chemotherapy continued to receive the combination as third-line treatment.

PFS from randomization to second-line progression or mortality in the intention-to-treat population served as the primary outcome.

At the time of the prespecified primary PFS analysis, median follow-up was 16.1 months in the combination arm and 15.9 months for those assigned chemotherapy alone.

Researchers reported significantly longer median PFS in the combination arm (6.3 months vs. 4.2 months; stratified HR=0.75; 95% CI, 0.61-0.93).

The rate of best objective response was 20.9% in the combination arm and 16.8% in the chemotherapy alone arm, a difference that was not statistically significant.

The rate of stable disease was markedly higher in the combination arm (48.9% vs. 33.5%). However, the median duration of response was longer among patients assigned chemotherapy alone (10.6 months vs. 8.3 months).

Serious adverse events occurred in 25% of patients assigned bevacizumab plus chemotherapy and 18% of those assigned chemotherapy alone.

Grade ≥3 adverse events included hypertension (13% in the combination arm vs. 7% in the chemotherapy alone arm), neutropenia (12% vs. 8%) and hand–foot syndrome (11% vs. 11%). Researchers observed grade 3 proteinuria in 7% of those assigned the combination regimen and <1% of those assigned chemotherapy alone.

“These results suggest that continued VEGF inhibition with further bevacizumab is a valid treatment option for patients with locally recurrent or metastatic HER-2–negative breast cancer whose disease was stabilized or responded to first-line bevacizumab with chemotherapy,” von Minckwitz and colleagues wrote.

For more information:

von Minckwitz G. Abstract #353O. Presented at: European Society for Medical Oncology Annual Congress; Sept. 26-30, 2014; Madrid.
von Minckwitz G. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)70439-5.

Disclosure: The researchers report funding or honoraria from, paid advisory or consultant roles with, stock ownership in and employment relationships with Roche. They also report honoraria from Celgene, Eisai, Lilly, Novartis and Pfizer.