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A Randomized Phase II Study of Immunization With Dendritic Cells Modified With Poxvectors Encoding CEA and MUC1 Compared With the Same Poxvectors Plus GM-CSF for Resected Metastatic Colorectal Cancer

Morse, Michael A. MD*; Niedzwiecki, Donna PhD; Marshall, John L. MD; Garrett, Christopher MD**; Chang, David Z. MD**; Aklilu, Mebea MD††; Crocenzi, Todd S. MD‡‡; Cole, David J. MD§§; Dessureault, Sophie MD‖‖; Hobeika, Amy C. PhD; Osada, Takuya MD; Onaitis, Mark MD; Clary, Bryan M. MD; Hsu, David MD*; Devi, Gayathri R. PhD; Bulusu, Anuradha; Annechiarico, Robert P.§; Chadaram, Vijaya§; Clay, Timothy M. PhD; Lyerly, H. Kim MD‡,§,‖

doi: 10.1097/SLA.0b013e318292919e
Randomized Controlled Trials

Objective: To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC).

Background: Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens.

Methods: Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study.

Results: Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ2 P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group.

Conclusions: Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142)

This study randomized patients with resected lung and liver metastases of colorectal cancer to either a poxvector-modified dendritic cell vaccine or a viral vector–based vaccine. Although there were no differences between the 2 vaccines, those who were vaccinated as part of the study experienced a survival advantage compared with contemporary, nonvaccinated patients.

Departments of *Medicine,

Biostatistics and Bioinformatics,

Surgery, Duke University Medical Center

§Duke Comprehensive Cancer Center,

Department of Immunology, Duke University Medical Center, Durham, NC

Georgetown University, Washington, DC

**MD Anderson Cancer Center, Houston, TX

††Wake Forest University Baptist Medical Center, Winston-Salem, NC

‡‡Earle Chiles Cancer Center, Providence Portland Medical Center, Portland, OR

§§Medical University of South Carolina, Charleston, SC

‖‖Moffitt Cancer Center, Tampa, FL. Dr Chang is now with Virginia Oncology Associates, Newport News, VA. Dr Clay is now with GlaxoSmithKline, Rixensart, Belgium.

Reprints: Michael A. Morse, MD, Department of Medicine, Room 403, MSRB 1, Box 3233, Duke University Medical Center, Durham, NC 27710. E-mail: morse004@mc.duke.edu.

Supported by NIH 2P01 CA078673-07 (PI: H. Kim Lyerly; Project PI: Michael Morse, MD) and by Golfers Against Cancer for aspects of the analysis. This trial is registered with ClinicalTrials.gov (NCT00103142).

Disclosure: The authors declare no conflicts of interest.

© 2013 by Lippincott Williams & Wilkins.