Continued bevacizumab improves second-line progression-free survival in women with bevacizumab pre-treated locally recurrent or metastatic breast cancer
Continued treatment with bevacizumab results in a significantly longer second-line progression-free survival (PFS) for women with locally recurrent or metastatic breast cancer (LR/mBC) after a bevacizumab containing first-line therapy, following latest results of the Phase III TANIA study.
Several randomised Phase III studies in HER2-negative LR/mBC previously showed significant improvements in PFS when bevacizumab was added to both first-line (E2100, AVADO, RIBBON-1) and second-line chemotherapy (RBBON-2). Sustained VEGF blockade may be important for long-term disease control given the critical role of VEGF throughout the angiogenic pathway and the fact that continuous VEGF suppression improved PFS and overall survival (OS) in preclinical models. In colorectal cancer, continued bevacizumab versus chemotherapy in second-line after first-line bevacizumab did already demonstrate to improve both OS and PFS. This outcome constituted the rationale for the open-label, randomised Phase III TANIA trial evaluating continued bevacizumab therapy in bevacizumab-pretreated LR/mBC patients.
In TANIA, a total of 494 patients with HER2-negative LR/mBC with progressive disease during, or after ≥12 weeks of first-line treatment with bevacizumab plus chemotherapy, were randomised 1:1 to second-line single-agent chemotherapy alone, or in combination with bevacizumab (15 mg/kg q3w or 10 mg/kg q2w). This second-line therapy was continued until disease progression, unacceptable toxicity or consent withdrawal. At progression, patients in the chemotherapy alone arm received third-line chemotherapy without bevacizumab, while patients initially randomised to chemotherapy plus bevacizumab received third-line chemotherapy plus bevacizumab. The primary endpoint was PFS from randomisation to second disease progression, or death. Additional endpoints included second-line PFS in prespecified subgroups, second- and third-line PFS, second-line objective response rate (ORR), overall survival (OS), safety and QoL.
The most frequently used second-line chemotherapy in the study was capecitabine (59% vs. 61%). The second-line PFS in the chemotherapy alone arm was 4.2 months versus 6.3 months in the chemotherapy plus bevacizumab arm (HR[95%CI]: 0.75 [0.61-0.93]; p = 0.0068). The overall response rate to second line therapy was 16.8% with chemotherapy alone compared to 20.9% with chemotherapy plus bevacizumab. Interestingly, a substantially higher proportion of patients in the bevacizumab arm obtained stable disease as compared to chemotherapy alone (48.9% vs. 33.5%).
Continuing bevacizumab was accompanied by some increased toxicity. The events seen were however in line with the known safety profile of bevacizumab. In fact, bevacizumab was associated with a higher incidence of grade 3/4 hypertension, neutropenia, proteinuria, leukopenia and febrile neutropenia.
In summary, the primary objective of the TANIA study was met, showing a statistically significant improvement in PFS with bevacizumab after disease progression on first-line bevacizumab-containing therapy. Second-line safety results were as expected from previous bevacizumab trials in LR/mBC. The final OS, second and third-line PFS and third-line safety results of this study are expected in 2015.
Von Minckwitz G, Puglisi F, Cortes J, et al. Efficacy and safety in TANIA, a randomised phase III trial of continued or reintroduced bevacizumab (BEV) after 1st-line BEV for HER2 negative, locally recurrent/metastatic breast cancer (LR/mBC). Presented at ESMO 2014; Abstract 353O.