Novel vaccine approaches: Prospects for PROSTVAC®-VF are bright

As research into novel vaccine approaches for treating advanced prostate cancer continues, one drug appears to be on the verge of blossoming, while another appears to be wilting, according to Leonard G. Gomella, MD.

Gomella, chairman of the Department of Urology and associate director of Clinical Affairs at Jefferson Kimmel Cancer Center, Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, said that immunotherapy is moving forward a year after sipuleucel-T (Provenge^®) became the first therapeutic vaccine approved by the Food and Drug Administration (FDA) for prostate cancer.

Dendreon, a company based in Seattle, Washington, custom-manufactures Provenge^® for patients by collecting their dendritic cells and culturing them with genetically engineered antigens.

Gomella said the most promising new prostate cancer vaccine in development is PROSTVAC^®-VF, which uses the smallpox viral vector to stimulate the immune system.

A randomized phase 2 clinical trial studied a prime-boost vaccine strategy using Vaccinia and fowlpox viruses (J Clin Oncol. 2004:22[11]:2122-2132).

In the study, 64 patients with biochemical progression after local therapy for prostate cancer received 1 of 3 vaccine combinations. At 19 months’ follow-up, 45.3% were free of prostate-specific antigen (PSA) progression and 78.1% evidenced clinical progression-free survival. Investigators said the most favorable results were found in those who had received a priming dose of Vaccinia-PSA.

In a subsequent study, Kantoff et al tested PROSTVAC^®-VF, comprised of Vaccinia and fowlpox viral vectors, with each encoding transgenes for PSA and 3 immune costimulatory molecules (B7-1, ICAM-1, and LFA3:TRICOM). The phase 2 trial involved 122 patients with metastatic castrate-resistant prostate cancer randomized 2:1 to receive the vaccine versus placebo (J Clin Oncol. 2009;27 [suppl 15]: abstract 5013).

The 82 patients who received the vaccine demonstrated an 8.5-month improvement in overall survival (OS). Gomella said the trial demonstrated a “statistically significant advantage” in OS with minimal adverse events, such as itching, fatigue, and chills.

“The bottom line is that this is a safe treatment,” Gomella said, “even though you’re using viral vectors.”

Bavarian Nordic, a biotechnology company headquartered in Denmark, is developing PROSTVAC^®-VF under an agreement with the National Cancer Institute. Clinical trials are continuing.

“This drug is working its way through the system and may offer us the next most viable therapeutic agent in the pipeline,” Gomella said.

GVAX Outlook Dimming

The outlook for GVAX, a whole-cell vaccine comprised of prostate cancer cell lines genetically modified to express tumor antigens, is not as promising, according to Gomella. He said the vaccine performed well in early studies but faltered in a large phase 3 trial, called VITAL-2, when it was compared in combination with docetaxel versus standard treatment of docetaxel plus prednisone. (ASCO Genitourinary Cancers Symposium, February 26-28, 2009; Orlando,FL, Abstract 7).

“The results were unimpressive,” Gomella said. “You did better with the standard treatment than you did combining this vaccine with the docetaxel. The future of GVAX is now in question and people think it may not be in play anymore.”

BioSante Pharmaceuticals Inc., based in Lincolnshire, Illinois, said on its Web site that research is continuing into the use of GVAX not only as a vaccine for treating prostate cancer but also against other cancers, with ongoing late-stage trials in progress for leukemia, myeloma, and breast cancer.