title: Phase II study of bevacizumab in combination with trastuzumab and capecitabine as first-line treatment for HER-2-positive locally recurrent or metastatic breast cancer.
abstract: 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/m2 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.
authors.affiliation: Hospital Gregorio Maraňon, Universidad Complutense, 28007 Madrid, Spain. mmartin@geicam.org
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
authors.forename: Anatoly
authors.initials: A
authors.lastname: Makhson
authors.forename: Joseph
authors.initials: J
authors.lastname: Gligorov
authors.forename: Mikhail
authors.initials: M
authors.lastname: Lichinitser
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semiglazov
authors.forename: Nana
authors.initials: N
authors.lastname: Scotto
authors.forename: Lada
authors.initials: L
authors.lastname: Mitchell
authors.forename: Sergei
authors.initials: S
authors.lastname: Tjulandin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab