title: Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence.
abstract: GP2 is a HER2-derived, HLA-A2+ restricted peptide. Phase I studies showed GP2 administered with GM-CSF to be safe and immunogenic. Here we report the primary analysis of a prospective, randomized, multicenter phase II adjuvant trial conducted to determine the vaccine's efficacy. The trial enrolled HLA-A2+, clinically disease-free, node-positive and high-risk node-negative breast cancer patients with tumors expressing HER2 (immunohistochemistry[IHC] 1+-3+). Patients were randomized to GP2+GM-CSF versus GM-CSF alone. Disease-free survival (DFS) was analyzed in intention-to-treat (ITT) and per-treatment cohorts; pre-specified subgroup analyses were performed for patients with IHC 3+ or FISH+ disease. The trial enrolled 180 patients; 89 received GP2+GM-CSF and 91 received GM-CSF alone. The groups were well-matched for clinicopathologic characteristics. Toxicities have been minimal. The Kaplan-Meier estimated 5-year DFS rate in the ITT analyses was 88% (95% CI:78-94%) in vaccinated vs. 81% (95% CI:69-89%) (P = 0.43) in control patients after a 34 month median follow-up. In the per-treatment analysis, the estimated 5-year DFS rates were 94% (95% CI:83-98%) and 85% (73-92%) (P = 0.17). In IHC 3+/FISH+ patients, the estimated 5-year DFS rate was 94% (82-98%) in vaccinated patients (n = 51) vs. 89% (71-96%) in control patients (n = 50), (P = 0.86) in the ITT analyses and 100% vs. 89% (71-96%) in vaccinated vs. control patients in the per-treatment analyses (P = 0.08). While the overall ITT analysis did not demonstrate benefit to vaccination, this trial confirmed that the GP2 vaccine is safe and suggests that vaccination may have clinical activity, particularly in patients with HER2 overexpression who received the full vaccine series (ie per-treatment group).
authors: Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Elizabeth A
authors: EA
authors: Mittendorf
authors: Cancer Immunology and Immunotherapy Center, St. Savas Cancer Hospital, Athens, Greece.
authors: Alexandros
authors: A
authors: Ardavanis
authors: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Jennifer K
authors: JK
authors: Litton
authors: Department of Hematology/Oncology, Brooke Army Medical Center, Ft. Sam Houston, TX, USA.
authors: Nathan M
authors: NM
authors: Shumway
authors: Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, TX, USA.
authors: Diane F
authors: DF
authors: Hale
authors: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: James L
authors: JL
authors: Murray
authors: Cancer Immunology and Immunotherapy Center, St. Savas Cancer Hospital, Athens, Greece.
authors: Sonia A
authors: SA
authors: Perez
authors: Cancer Vaccine Development Laboratory, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Sathibalan
authors: S
authors: Ponniah
authors: Cancer Immunology and Immunotherapy Center, St. Savas Cancer Hospital, Athens, Greece.
authors: Constantin N
authors: CN
authors: Baxevanis
authors: Cancer Immunology and Immunotherapy Center, St. Savas Cancer Hospital, Athens, Greece.
authors: Michael
authors: M
authors: Papamichail
authors: Cancer Vaccine Development Program, San Antonio, TX, USA.
authors: George E
authors: GE
authors: Peoples
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D016037:Single-Blind Method; D015996:Survival Rate; D014611:Vaccination; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D022223:Vaccines, Subunit
keywords: HER2; breast cancer; cytotoxic T lymphocytes; trastuzumab; vaccine