Abstract P5-01-05: Personalized peptide vaccines in combination with conventional chemo- or endocrine therapy for metastatic breast cancer: A single-arm phase II study

Abstract

Abstract Background: Immunotherapy using multiple personalized peptide vaccines (PPV) has been reported to be effective for boosting anticancer immunity in patients (pts) with advanced prostate cancer and glioblastoma. The PPVs binding HLA-A2, A24, A3 family and A26 molecules were selected from 31 candidate peptides derived from various tumor associated antigens. Currently, we performed a phase II trial to evaluate the benefit of the PPVs in combination with conventional chemo-or endocrine therapy for pretreated metastatic breast cancer (MBC). Methods: Seventy-one pretreated pts had histologically confirmed measurable MBC and their HLA A molecules matched each of HLA-A2, A24, A26 and A3 family. Pre-vaccination plasma was measured for their IgG levels reactive to each of 31 peptides followed by administration subcutaneously of the four peptides at maximum showing higher levels of IgG in order with schedule of every 1-2 week. The concurrent conventional chemotherapy or endocrine therapy was available for the combination of PPVs. The primary endpoint was anti-tumor immunologic effect and safety, and the secondary endpoints were clinical responses and survival. Levels of IgG reactive to each of the 31 peptides in the pre- and post-treatment plasma at every 6 times of vaccination were measured using LUMNEX system. The CTL responses were simultaneously evaluated using ELISPOT method. Clinical response was evaluated by RECIST criteria. Results: Between May 2009 and December 2012, a total of 71 pts (Luminal-Her2- cases: 39; Her2+cases: 18; Triple negative(TN) cases:14) were enrolled in this study. The median duration of follow-up was 20.7 months. Concurrent chemotherapies (capecitabine, gemcitabine, eribulin, vinorelbine etc.) and endocrine therapies (aromatase inhibitor, toremifen or fulvestrant) were administered to 36 and 24 pts, respectively. Trastuzumab, Laptinib or Bevacizumab was simultaneously used for 13 pts. After 6th vaccination, the IgG reaction and CTL response were identified in 53 of 71 (74.6%) pts and 33 of 63 (52.3%) pts. There were no significant differences between TN cases and the other cases of MBC with regard to immunological humoral and/or cellular responses. No vaccine-related severe adverse events were observed. Clinical response rate of assessable 61 pts was 14.8% (CR 3, PR 6, SD 24, PD 28). The median PFS and OS were 7.6 m and 20.7 m, respectively. In contrast, the PFS and OS of luminal type, Her2 type or TN type were 12, 4.6 or 8.3 m and 24, 15 or 12 m. Conclusions: The phase II PPVs study for MBC demonstrated the promising response and safety, and further studies are essential to identify the clinical benefits of this novel therapy. Clinical trial information: UMIN000001482. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-01-05.