Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence

Autor: Sathibalan Ponniah, Tommy A. Brown, Diane F. Hale, Constantin N. Baxevanis, N. F. Pistamaltzian, John W. Myers, Kaitlin M. Peace, Eleftheria A. Anastasopoulou, Doreen O. Jackson, Jennifer K. Litton, James L. Murray, Michael Papamichail, Nathan M. Shumway, James T. Symanowski, George E. Peoples, Alexandros Ardavanis, Elizabeth A. Mittendorf, Sonia A. Perez, Timothy J. Vreeland, Julia M. Greene, G. Travis Clifton
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Cancer Research
Receptor
ErbB-2
medicine.medical_treatment
Disease
law.invention
0302 clinical medicine
Breast cancer
Randomized controlled trial
law
Single-Blind Method
Prospective Studies
skin and connective tissue diseases
Carcinoma
Ductal
Breast
Middle Aged
Prognosis
Clinical Trial
Gene Expression Regulation
Neoplastic
Survival Rate
Receptors
Estrogen
030220 oncology & carcinogenesis
Vaccines
Subunit
Female
Immunotherapy
Receptors
Progesterone
Adult
medicine.medical_specialty
Subgroup analysis
Breast Neoplasms
03 medical and health sciences
Internal medicine
HER2
medicine
Biomarkers
Tumor
Humans
In patient
Neoplasm Invasiveness
AE37
business.industry
GP2
Significant difference
medicine.disease
Peptide Fragments
Carcinoma
Lobular
030104 developmental biology
Landmark analysis
Neoplasm Recurrence
Local
business
Vaccine
Follow-Up Studies
Zdroj: Breast Cancer Research and Treatment
ISSN: 1573-7217
0167-6806
Popis: Purpose AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis. Methods In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated. Results 456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275–1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499–1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114–1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142–0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG. Conclusions This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.
Databáze: OpenAIRE
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