Survival advantage in patients with metastatic breast cancer receiving endocrine therapy plus Sialyl Tn-KLH vaccine: post hoc analysis of a large randomized trial.

Background: A multicenter, double blinded, randomized phase III trial of the therapeutic cancer vaccine STn-KLH was completed in an international cohort of 1,028 women with metastatic breast cancer who had either no evidence of disease or nonprogressive disease following first-line chemotherapy. This trial is registered with ClinicalTrials.gov (No. NCT00003638 ). The outcomes showed that STn-KLH was safe and relatively well tolerated but had neither a positive nor negative effect on time to progression (TTP) or overall survival (OS) duration in the intent-to-treat population when compared with KLH control alone. The purpose of this post hoc analysis is to explore the potential benefit of combining an antiestrogen with MUC1 vaccines in metastatic breast cancer patients. Methods: The data were further explored to determine if a retrospective, reassigned endocrine subset patient stratification produces subgroups that may have experienced benefit in TTP or survival compared with the phase III trial ITT analysis. Results: Women treated with concomitant endocrine therapy, a pre stratified subset comprising approximately one third of the original study population, achieved a clinical benefit both in terms of TTP and survival compared with women who did not receive endocrine therapy. Moreover, women in the endocrine-treatment subset who mounted a median or greater antibody response (titer >1:320 toward bovine submaxillary mucin) to the STn-KLH vaccine experienced significantly longer median survival than their trial counterparts who mounted a below-median antibody response. Conclusion: Unlike maintenance chemotherapy, with its associated cumulative toxicity, the combination of endocrine and STn-KLH therapy may offer clinical benefit with few adverse effects for women with metastatic breast cancer. [ABSTRACT FROM AUTHOR]