LBA14 - A phase 2 randomized trial of docetaxel alone or in combination with therapeutic cancer vaccine, CEA-, MUC-1-TRICOM
|Date||01 October 2012|
|Event||ESMO Congress 2012|
|Session||Breast cancer, locally advanced and metastatic|
C. Heery1, N. Ibrahim2, R.A. Madan3, M. Mohebtash4, P. Arlen1, S. McMahon1, S. Hodge2, S.M. Steinberg5, J. Schlom6, J. Gulley7
AbstractBackground: A previous phase 1/2 trial of PANVAC, a poxviral based cancer vaccine, suggested clinical efficacy in some patients ( pts) with breast and ovarian cancer and evidence of immunologic activity. Preclinical data showed DOC can
modify tumor phenotype, making tumor cells more amenable to T-cell mediated killing. The goal was to determine if DOC and PANVAC could synergize and improve clinical outcomes compared with DOC alone.
Methods: This is an open-label randomized phase 2 multi-center trial designed to enroll 48 pts with metastatic breast cancer to receive DOC in combination with PANVAC (A) or alone (B). Cross-over was allowed so that pts randomized to B could receive the vaccine upon progression. Eligibility included ECOG performance status 1 and normal organ and immune function with no limits on previous lines of therapy, but pts may not have received DOC for metastatic disease. Her2+ pts on trastuzumab were allowed to continue trastuzumab on imtris;al. All pts received DOC 35 mg/m2 weekly × 3 doses during 28-day
cycles. Pts on A were “primed” with recombinant vaccinia-PANVAC study day 1. Three weeks later, they began 28-day cycles of DOC with “boost” recombinant fowlpox-PANVAC given on day 1, given until progression. CT and bone scans were performed after 3 cycles and then every 2 cycles. 1° endpoint was PFS. 2° endpoints included overall survival and immunologic correlative studies.
Results: Enrollment of 48 pts completed in February 2012 (A, n = 25; B, n = 23). Five pts remain on treatment (2 on A, 3 on B). Patient and tumor characteristics were well matched. Analysis through August 2, 2012 (median follow-up of 5.1 months for
pts on study), indicates PFS is 6.6 vs. 3.8 months in A vs. B (p = 0.12, HR = 0.67, 95% CI: 0.34 to 1.31) Toxicity was similar in both arms. Immune analysis and correlation to pt clinical outcomes is ongoing.
Conclusion: This randomized study suggests the combination of PANVAC with DOC in metastatic breast cancer may provide a clinical benefit compared to DOC alone. The clear separation of the curves indicates potential benefit, which is not
statistically significant, likely due to the small number of pts enrolled. This study was hypothesis generating and may provide both rationale and statistical assumptions for a larger definitive randomized study.
Acknowledgements: M. Bilusic, J. Kim, N.K. Singh, J. Hodge. Clinical trials.gov number: NCT00179309.
Disclosure: J. Schlom: The Laboratory of Tumor Immunology and Biology, of which I am Lab Chief, has a Collaborative Research and Development Agreement with Bavarian Nordic. The LTIB’s research is funded by the Intramural Research Program, CCR, NCI, NIH. All other authors have declared no conflicts of interest.