title: Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer.
abstract: In order to examine the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-P) in combination with bevacizumab (B) and gemcitabine (G) for the first-line treatment of patients with HER2-negative metastatic breast cancer (MBC). In this single-center, open-label phase II trial, patients with HER2-negative MBC received gemcitabine 1500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg (each administered intravenously) on days 1 and 15 of a 28-day cycle. The primary end point was progression free survival (PFS); secondary end points were overall response rate (ORR), complete (CR) and partial (PR) response rates, clinical benefit (ORR + stable disease), overall survival (OS), and safety. Thirty patients were enrolled. One patient was ineligible and was not included in analysis. Median PFS was 10.4 months (95% CI: 5.6-15.2 months). ORR was 75.9%, comprising eight (27.6%) CRs and 14 (48.3%) PRs; five patients had stable disease (SD) and two patients (6.9%) had progressive disease (PD) as their best response. The clinical benefit rate was 93.1% (27/29) in the overall group and 84.6% in the triple-negative cohort (11/13). The 18-month survival rate was 77.2% (95% CI: 51.1-90.5%). Eight (27.6%) patients experienced grade 3 or 4 toxicity: grade 4 neutropenic fever (n = 1) and grade 3 infection (n = 6), leukopenia, thrombocytopenia, peripheral neuropathy, seizure, shortness of breath, hematuria, and cardiac tamponade (one each). First-line therapy with nab-P, B, and G demonstrated a median PFS of 10.4 months and a 75.9% ORR with acceptable toxicity; this novel combination warrants investigation in a randomized study.
authors.affiliation: Florida Cancer Specialists and Research Institute, Gainesville, FL, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lobo
authors.forename: Gilberto
authors.initials: G
authors.lastname: Lopes
authors.forename: Odalys
authors.initials: O
authors.lastname: Baez
authors.forename: Aurelio
authors.initials: A
authors.lastname: Castrellon
authors.forename: Annapoorna
authors.initials: A
authors.lastname: Ferrell
authors.forename: Connie
authors.initials: C
authors.lastname: Higgins
authors.forename: Erin
authors.initials: E
authors.lastname: Hurley
authors.forename: Judith
authors.initials: J
authors.lastname: Hurley
authors.forename: Isildinha
authors.initials: I
authors.lastname: Reis
authors.forename: Stephen
authors.initials: S
authors.lastname: Richman
authors.forename: Pearl
authors.initials: P
authors.lastname: Seo
authors.forename: Orlando
authors.initials: O
authors.lastname: Silva
authors.forename: Joyce
authors.initials: J
authors.lastname: Slingerland
authors.forename: Keleni
authors.initials: K
authors.lastname: Tukia
authors.forename: Catherine
authors.initials: C
authors.lastname: Welsh
authors.forename: Stefan
authors.initials: S
authors.lastname: Glück
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018567:Breast Neoplasms, Male / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005431:Florida; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000418:Albumins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003841:Deoxycytidine; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000093542:Gemcitabine; C520255:130-nm albumin-bound paclitaxel; C508053:ERBB2 protein, human