Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence
| Autor: | Eleftheria A. Anastasopoulou, Alexandros Ardavanis, N. F. Pistamaltzian, George E. Peoples, Constantin N. Baxevanis, Diane F. Hale, Nathan M. Shumway, James L. Murray, Michael Papamichail, Sonia A. Perez, James T. Symanowski, Jennifer K. Litton, Sathibalan Ponniah, E. von Hofe, Elizabeth A. Mittendorf |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
0301 basic medicine Relative risk reduction Oncology medicine.medical_specialty Receptor ErbB-2 medicine.medical_treatment Phases of clinical research Triple Negative Breast Neoplasms Cancer Vaccines Disease-Free Survival law.invention 03 medical and health sciences 0302 clinical medicine Breast cancer Adjuvants Immunologic Randomized controlled trial law Internal medicine medicine Humans Triple-negative breast cancer Aged business.industry Original Articles Hematology Middle Aged medicine.disease Peptide Fragments Confidence interval Vaccination 030104 developmental biology 030220 oncology & carcinogenesis Immunology Female Neoplasm Recurrence Local business Adjuvant |
| Zdroj: | Annals of Oncology. 27:1241-1248 |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdw150 |
| Popis: | Background AE37 is the Ii-Key hybrid of the MHC class II peptide, AE36 (HER2 aa:776–790). Phase I studies showed AE37 administered with granulocyte macrophage colony-stimulating factor (GM-CSF) to be safe and highly immunogenic. A prospective, randomized, multicenter phase II adjuvant trial was conducted to evaluate the vaccine's efficacy. Methods Clinically disease-free node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 [immunohistochemistry (IHC) 1–3+] were enrolled. Patients were randomized to AE37 + GM-CSF versus GM-CSF alone. Toxicity was monitored. Clinical recurrences were documented and disease-free survival (DFS) analyzed. Results The trial enrolled 298 patients; 153 received AE37 + GM-CSF and 145 received GM-CSF alone. The groups were well matched for clinicopathologic characteristics. Toxicities have been minimal. At the time of the primary analysis, the recurrence rate in the vaccinated group was 12.4% versus 13.8% in the control group [relative risk reduction 12%, HR 0.885, 95% confidence interval (CI) 0.472–1.659, P = 0.70]. The Kaplan–Meier estimated 5-year DFS rate was 80.8% in vaccinated versus 79.5% in control patients. In planned subset analyses of patients with IHC 1+/2+ HER2-expressing tumors, 5-year DFS was 77.2% in vaccinated patients (n = 76) versus 65.7% in control patients (n = 78) (P = 0.21). In patients with triple-negative breast cancer (HER2 IHC 1+/2+ and hormone receptor negative) DFS was 77.7% in vaccinated patients (n = 25) versus 49.0% in control patients (n = 25) (P = 0.12). Conclusion The overall intention-to-treat analysis demonstrates no benefit to vaccination. However, the results confirm that the vaccine is safe and suggest that vaccination may have clinical benefit in patients with low HER2-expressing tumors, specifically TNBC. Further evaluation in a randomized trial enrolling TNBC patients is warranted. |
| Databáze: | OpenAIRE |
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