Survival Advantage in Patients with Metastatic Breast Cancer Receiving Endocrine Therapy plus Sialyl Tn-KLH Vaccine: Post Hoc Analysis of a Large Randomized Trial

Abstract

Background: A multicenter, double blinded, randomized phase III trial of the therapeutic cancer vaccine sialy1-Tn (STn) conjugated to keyhole-limpet Hemocyanin (KLH) was completed in an international cohort of 1,028 women with metastatic breast cancer who had nonprogressive disease or no evidence of disease after first-line chemotherapy (ClinicalTrials.gov, (NCT00003638). STn-KLH was safe and relatively well tolerated but did not affect time to progression (TTP) or overall survival (OS) duration. The purpose of this post hoc analysis was to explore whether patients who received concurrent endocrine therapy and STn-KLH had a TTP or OS benefit.

Methods: A retrospective, blinded review of the data from the phase III trial of STn-KLH was performed to ensure that strata assignments were appropriate. We then studied the effect of concomitant endocrine therapy and STn-KLH or KLH on TTP and OS in the cohort described above. We also assessed the TTP and OS by antibody responses in patients who received endocrine therapy.

Results: The women treated with concomitant endocrine therapy, a pre-stratified subset comprising approximately one-third of the original study population, and STn-KLH had longer TTP and OS than the control group of women who received KLH alone. Moreover, of the women who received endocrine therapy, those who had a median or greater antibody response (titer >1:320 toward ovine sub maxillary mucin) to the STn-KLH vaccine had significantly longer median OS than those who had a below-median antibody response.

Conclusion: Adding STn-KLH to endocrine therapy may improve clinical outcomes with few adverse effects for women with metastatic breast cancer.

Keywords: keyhole-limpet Hemocyanin; metastatic breast cancer; sialy1-Tn.

Conflict of interest statement

Competing Interests: See funding information in Acknowledgments.

Figures

Figure 1

Overall survival curves of participants who received endocrine therapy plus STn-KLH (red) or KLH (black).

Figure 2

Overall survival curves by antibody response for patients who received endocrine therapy with STn-KLH (A) or with KLH (B) (sponsor-defined subset). A) Patients whose α-anti ovine submaxillary mucin immunoglobulin G titer was equal to or greater than the median (red) survived significantly longer than those whose titer was less than the median (black) P =. 0092); B) For KLH titer, the difference in survival was not significant P =. 26.

Figure 3

Overall survival curves by type of endocrine therapy (SERM or AI) in patients who received STn-KLH or KLH. Patients in the selective estrogen receptor modulator group (red) survived longer than those in the aromatase inhibitor group (black). The difference between the groups that received STn-KLH was not significant (A), but a substantial [but not significant] difference was seen between the groups [A] that received KLH (the control vaccine) (B).