title: SWOG S0800 (NCI CDR0000636131): addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer.
abstract: SWOG S0800, a randomized open-label Phase II clinical trial, compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide (AC) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). Patients were randomly allocated (2:1:1) to three neoadjuvant chemotherapy arms: (1) nab-paclitaxel with concurrent bevacizumab followed by AC; (2) nab-paclitaxel followed by AC; or (3) AC followed by nab-paclitaxel. The primary endpoint was pathologic complete response (pCR) with stratification by disease type (non-IBC LABC vs. IBC) and hormone receptor status (positive vs. negative). Overall survival (OS), event-free survival (EFS), and toxicity were secondary endpoints. Analyses were intent-to-treat comparing bevacizumab to the combined control arms. A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer (TNBC). The addition of bevacizumab significantly increased the pCR rate overall (36 vs. 21 %; p = 0.019) and in TNBC (59 vs. 29 %; p = 0.014), but not in hormone receptor-positive disease (24 vs. 18 %; p = 0.41). Sequence of administration of nab-paclitaxel and AC did not affect the pCR rate. While no significant differences in OS or EFS were seen, a trend favored the addition of bevacizumab for EFS (p = 0.06) in TNBC. Overall, Grade 3-4 adverse events did not differ substantially by treatment arm. The addition of bevacizumab to nab-paclitaxel prior to dose-dense AC neoadjuvant chemotherapy significantly improved the pCR rate compared to chemotherapy alone in patients with triple-negative LABC/IBC and was accompanied by a trend for improved EFS. This suggests reconsideration of the role of bevacizumab in high-risk triple-negative locally advanced breast cancer.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX, USA. zeina.nahleh@ttuhsc.edu.
authors.forename: Z A
authors.identifier: 0000-0002-2489-1501
authors.initials: ZA
authors.lastname: Nahleh
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Barlow
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Hayes
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Schott
authors.affiliation: Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Gralow
authors.affiliation: Women and Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Sikov
authors.affiliation: Genentech, Inc., San Francisco, CA, USA.|Mayo Clinic, Jacksonville, FL, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Hematology Oncology Consultants, Inc., Westerville, OH, USA.|Columbus NCI Community Oncology Research Program, Columbus, OH, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chennuru
authors.affiliation: Loma Linda University Cancer Center, Loma Linda, CA, USA.
authors.forename: H R
authors.initials: HR
authors.lastname: Mirshahidi
authors.affiliation: Gibbs Cancer Center and Research Institute/Southeast Clinical Oncology Research (SCOR) Consortium NCORP/Upstate Carolina CCOP (previous), Spartanburg, SC, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Corso
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Lew
authors.affiliation: Yale University, New Haven, CT, USA.
authors.forename: L
authors.initials: L
authors.lastname: Pusztai
authors.affiliation: Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Livingston
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000068258:Bevacizumab; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel
keywords: Bevacizumab; Breast cancer; Inflammatory; Locally advanced; Neoadjuvant