Open AccessPhase II Study of Bevacizumab in Combination with Trastuzumab and Capecitabine as First‐Line Treatment for HER‐2‐positive Locally Recurrent or Metastatic Breast Cancer
Author(s) -
Martín Miguel,
Makhson Anatoly,
Gligorov Joseph,
Lichinitser Mikhail,
Lluch Ana,
Semiglazov Vladimir,
Scotto Nana,
Mitchell Lada,
Tjulandin Sergei
Publication year - 2012
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2011-0344
Subject(s) - medicine , capecitabine , bevacizumab , metastatic breast cancer , trastuzumab , adverse effect , clinical endpoint , breast cancer , oncology , phases of clinical research , gastroenterology , surgery , cancer , toxicity , chemotherapy , clinical trial , colorectal cancer
We report the first results from a phase II, open‐label study designed to evaluate the efficacy and safety of bevacizumab in combination with trastuzumab and capecitabine as first‐line therapy for human epidermal growth factor receptor (HER)‐2‐positive locally recurrent (LR) or metastatic breast cancer (MBC). Patients were aged ≥18 years with confirmed breast adenocarcinoma, measurable LR/MBC and documented HER‐2‐positive disease. Patients received bevacizumab (15 mg/kg on day 1) plus trastuzumab (8 mg/kg on day 1 of cycle 1, 6 mg/kg on day 1 of each subsequent cycle) plus capecitabine (1,000 mg/m 2 twice daily, days 1–14) every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. Eighty‐eight patients were enrolled; 40 (46%) are still on study treatment. The median follow‐up was 8.8 months (range, 0.9–17.1 months). The overall response rate, the primary endpoint, was 73% (95% confidence interval [CI], 62%–82%), comprising 7% complete and 66% partial responses. The median progression‐free survival interval was 14.4 months (95% CI, 10.4 months to not reached [NR]), with 35 events. The median time to progression was 14.5 months (95% CI, 10.5 months to NR), with 33 events. Treatment was well tolerated; main side effects were grade 3 hand–foot syndrome (22%), grade ≥3 diarrhea (9%), and grade ≥3 hypertension (7%). Overall, 44% of patients experienced grade ≥3 treatment‐related adverse events and 13 patients discontinued capecitabine because of toxicity, but continued with bevacizumab and trastuzumab. Heart failure was seen in two patients. The combination of bevacizumab, trastuzumab, and capecitabine was clinically active as first‐line therapy for patients with HER‐2‐positive MBC, with an acceptable safety profile and no unexpected toxicities.