Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial

Abstract

Patients with metastatic triple-negative breast cancer (TNBC) typically have a poor prognosis and limited treatment options. To determine the impact of combining bevacizumab with second-line chemotherapy in patients with metastatic TNBC, we performed an exploratory subgroup analysis of the randomized phase 3 RIBBON-2 trial. RIBBON-2 enrolled patients with metastatic breast cancer that had progressed on first-line non-bevacizumab-containing chemotherapy. After selection of chemotherapy (taxane, gemcitabine, capecitabine, or vinorelbine), patients were randomized 2:1 to receive chemotherapy with either bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Of 684 patients treated in RIBBON-2, 159 (23%) had TNBC. Baseline characteristics were reasonably balanced in the two treatment groups. The majority received taxane chemotherapy. The hazard ratio (HR) for PFS was 0.494 [95% confidence interval (CI) 0.33-0.74; P = 0.0006]. Median PFS was 6.0 months with bevacizumab-chemotherapy versus 2.7 months with chemotherapy alone. Median OS was 17.9 versus 12.6 months, respectively (HR 0.624, 95% CI 0.39-1.007; P = 0.0534). ORR was 41 versus 18%, respectively (P = 0.0078). The safety profile was consistent with the overall study population and previous phase 3 trials of bevacizumab. Patients with metastatic TNBC derived significant PFS and response benefits from the combination of bevacizumab with second-line chemotherapy. Despite the small sample size and immature data, there was a trend toward improved OS.

Triple-Negative Breast Cancer Patients Treated at MD Anderson Cancer Center in Phase I Trials: Improved Outcomes with Combination Chemotherapy and Targeted Agents

“…Our results are consistent with previously published studies of patients with TNBC treated with a combination including an anti-angiogenic agent that reported improved response (SD≥6 months/PR/CR) in the neoadjuvant setting and prolonged PFS in patients with metastatic disease (25-28). Several studies have demonstrated that the addition of bevacizumab to neoadjuvant chemotherapy improved pathological CR rate in early and locally resectable TNBC (25, 26).…”

A phase II trial of biweekly vinorelbine and oxaliplatin in second- or third-line metastatic triple-negative breast cancer

“…Taking into account the prior exposure of taxane and/or cisplatin, NVBOX regimen was considered reasonably well tolerated. Although cytotoxic chemotherapy remains the mainstay of treatment for mTNBC, chemotherapy combined with targeted agents such as PARP inhibitors, 11 EGFR inhibitors, 12,13 antiangiogenic agents 40 and Chk1 inhibitor 41 were recently investigated in the later-line setting, some of which 11,13,40 showed gains in response rate and PFS and were worthy of being further explored.…”

Targeted Therapies in Triple-Negative Breast Cancer

“…A trend towards an improved OS for the TNBC cohort (17.9 vs. 12.6 months, p = 0.0534), in addition to a significant PFS benefit (6.0 vs. 2.7 months; hazard ratio 0.45; p = 0.0006), was observed only in an explorative subgroup analysis of the randomized phase III second-line trial, RIBBON-2 [41]. However, this can at best be regarded as a hypothesis-generating retrospective analysis due to small number of patients (n = 159) and statistical considerations.…”