Immunotherapy with MUC1/CEA vaccine alone or combined with chemotherapy in patients with metastatic breast cancer.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #4123 Background: PANVAC is a recombinant pox viral vaccine that contains transgenes for the tumor-associated antigens (TAAs), MUC1 and CEA. PANVAC also contains three T-cell co-stimulatory molecules (B7.1, LFA-3, ICAM-1) to enhance immune response. Clinical studies with a similar vaccine have shown docetaxel does not diminish specific T-cell responses to the TAAs delivered in the pox viral vaccines. We are evaluating the use of PANVAC in two ongoing trials in patients with metastatic breast cancer. Methods: The primary end point of these two phase II trials is progression-free survival (PFS). As secondary end point specific T-cell response is measured using ELISPOT assay in HLA-A2 patients. One study uses vaccine alone, given monthly by SC injections and is accompanied by 4 days of low dose GM-CSF. The other trial randomizes to either vaccine + docetaxel or docetaxel alone; giving the same V regimen (as the first study) on day 1 followed by docetaxel at 35 mg/m2 on days 2, 9, and 16 of each 28 day cycle. The chemotherapy alone arm uses the same docetaxel dosing. Results: Twenty three patients have been accrued with a median age of 57.6 (31-75) years. Sixteen patietns had ER/PR+ tumors. The patients had a median of 4 (0-6) previous chemotherapy regimens; their median time since their last chemotherapy was 2 months with a 10th – 90th percentile of 1-8 months. Vaccine is well tolerated with few grade 3 and no grade 4 adverse events. Most of the grade 1-2 toxicities were self-limited site reactions and flu-like symptoms. Three of 13 patients on vaccine alone study have shown measurable clinical benefits. Two were on study for 6 months, of whom one had significant improvement in pain with reduction in vertebral lesions on MRI; another had a sustained >20% decrease in bulky liver metastases. A third patient on vaccine alone was on study for 9 months with reduction in her mediastinal lymphadenopathy. Of the 6 patients who received vaccine + docetaxel, 5 had measurable disease. One achieved PR by RECIST criteria and remained on study for 19 months; another had a 50% reduction in the diameter of a chest wall lesion. A third patient with bone only disease was on study for 12 months with significant improvements on her bone scan. Conclusions: Vaccine given alone or in combination with docetaxel is shown to be safe in patient with metastatic breast cancer. There is preliminary evidence that there may be some clinical benefit from vaccine alone as well as its combination with chemotherapy. Confirmation of these results and PFS determination requires additional patient enrollment and follow up in both studies. Furthermore, immunologic studies including functional analysis of CD4 and CD8 T-cells will be performed to help elucidate the immune responses these regimens may elicit. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4123.