Optimizing Postneoadjuvant Treatment of Residual Breast Cancer With Adjuvant Bevacizumab Alone, With Metronomic or Standard-Dose Chemotherapy: A Combined Analysis of DFCI 05-055 and DFCI 09-134/TBCRC 012/ABCDE Clinical Trials.

Background: Breast cancer patients with residual disease after neoadjuvant therapy have increased risk of recurrence. Novel therapies to decrease this risk are urgently needed.

Methods: Two clinical trials (05-055 and 09-134) offered adjuvant bevacizumab-based therapy to stage I-III breast cancer patients with residual disease after neoadjuvant chemotherapy. Study 05-055 evaluated four treatment regimens: bevacizumab (cohort A); bevacizumab with metronomic cyclophosphamide and methotrexate (CM) (cohort B); and bevacizumab with body surface area-dosed capecitabine (cohorts C); or flat-dosed capecitabine (cohort D). The primary endpoint was feasibility and tolerability. In 09-134, patients were randomized to bevacizumab with or without CM; the primary endpoint was recurrence-free survival (RFS). Study 09-134 closed prematurely for lack of accrual. A pooled survival analysis with participants from 05-055 and 09-134 was conducted.

Results: Among 213 total patients (05-055, n = 163; 09-134, n = 50), the most common adverse events (AEs) of any grade were headache (49.3%) and fatigue (57.3%). Grade 3-4 AEs were highest in cohorts C (71.4%) and D (72.5%). The 36-month RFS was 58.0% with bevacizumab monotherapy, 62.3% with bevacizumab plus CM, and 72.7%-75.0% with bevacizumab plus capecitabine (depending on schedule). Treatment with capecitabine was independently associated with improved RFS in triple-negative breast cancer (TNBC) (HR: 0.47; 95% CI, 0.23-0.96).

Conclusion: This pooled analysis demonstrates that postneoadjuvant bevacizumab plus capecitabine may be associated with improved RFS, especially in TNBC. Each regimen carries moderate toxicity, and despite these treatments, patients with residual disease after neoadjuvant therapy still experience high rates of recurrence, indicating that new strategies are warranted.

Clinical Trial Registration: clinicaltrials.gov, NCT00121134 (DFCI Protocol Number: 05-055); NCT00925652 (DFCI Protocol Number: 09-134).