Leonard G. Gomella, MD
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 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 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 II clinical trial studied a prime-boost vaccine strategy using Vaccinia and fowlpox viruses (J Clin Oncol. 2004;22:2122-2132
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 II trial involved 122 patients with metastatic castration-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 comprising 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 III 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.”
On April 18, changes in GVAX licensing underscored Gomella’s assessment. BioSante Pharmaceuticals Inc announced that it had licensed the vaccine to Aduro BioTech, a clinicalstage company, in exchange for future milestone and royalty payments. Aduro said it would proceed initially with developing the GVAX vaccine for the treatment of pancreatic cancer.