Clinical Review Abstract
Trials in Progress Abstract
Abstracts selected for publication but not presentation at the Annual Meeting
Abstracts granted an exception in accordance with ASCO's Conflict of Interest Policy
Safety profile of recombinant poxviral TRICOM vaccines.
Genitourinary (Prostate) Cancer
2013 ASCO Annual Meeting
J Clin Oncol 31, 2013 (suppl; abstr e16036)
Author(s): Joseph W. Kim, Jennifer L. Marte, Nishith K. Singh, Christopher Ryan Heery, Ravi Amrit Madan, Mary Pazdur, Sheri McMahon, Myrna Rauckhorst, Jeffrey Schlom, Philip W. Kantoff, James L. Gulley; Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; Laboratory of Tumor Immunology and Biology, Medical Oncology Branch, National Cancer Institute, Bethesda, MD; Medical Oncology Branch, National Cancer Institute, Bethesda, MD; Laboratory of Tumor Immunology and Biology, Center for Cancer Research, Bethesda, MD; Dana-Farber Cancer Institute, Boston, MA
Background: Recombinant (rec) poxviruses have been developed as therapeutic cancer vaccines. A multi-institutional, randomized phase II trial of poxviral vaccine, PROSTVAC-V/F, suggested an improvement in median overall survival in men with metastatic castration resistant prostate cancer. A phase III trial in this same population is accruing. Accumulating data suggest a favorable safety profile of the poxviral vaccines (vacs). Methods: We reviewed all vaccine injections (inj) from 297 patients (pts) in 9 clinical trials involving poxviral vaccines. Vacs consisted of rec vaccinia and rec fowlpox encoded with 3 human costimulatory molecules (TRICOM), and a) prostate specific antigen, or b) carcinoembryonic antigen +/-mucin-1. Vacs were administered at doses between 1.2x108 to 2x109 pfu, subcutaneously, in all pts. 21 pts were also vaccinated intra-tumorally. 84 pts received concurrent treatments, such as radiation, celecoxib, ipilimumab, samarium-153, or flutamide in 4 of these trials. All 9 trials involved granulocyte-macrophage colony-stimulating factor (GM-CSF), or rec fowlpox encoding GM-CSF as an immune adjuvant. We report the grade >=2 adverse events (AEs) at least possibly attributed to vaccine. Results: A total of 1,793 poxviral inj were given. 33% (593) of all inj were associated with grade >=2 vaccination emergent AEs. Of those, 25.3 % (454) were local inj site reactions; none serious. There was no contact transmission or inadvertent inoculation. One patient experienced grade 4 myocardial infarction and thrombotic thrombocytopenic purpura (TTP) reported as possibly related to vaccine. Below is the summary of AEs. Conclusions: Recombinant poxviral TRICOM vaccines appear safe and well tolerated at a broad range of doses, routes of administration and in combination with other treatments. Clinical trial information: NCT00081848, NCT00088413, NCT00060528, NCT00060528, NCT00078585, NCT00096551, NCT00113984.
|AEs||Grade (G) 2||G 3||G 4||% of injections
associated with an AE
|Injection site reaction||454||0||0||25.3|
|Injection site cellulitis||0||2||0||0.1|
|General (fatigue, myalgia, rash, etc.)||53||7||0||3.3|
|Respiratory (dyspnea, etc.)||4||2||0||0.3|
|Gastrointestinal (nausea, etc.)
|Neurologic (headache, etc.)||9||2||0||0.6|
Other Abstracts in this Sub-Category:
1. Clinical outcomes in patients with castrate-refractory prostate cancer (CRPC) metastatic to bone randomized in the factorial TRAPEZE trial to docetaxel (D) with strontium-89 (Sr89), zoledronic acid (ZA), neither, or both (ISRCTN 12808747).