Cancer vaccines: can they improve survival?
In patients with metastatic cancer, therapeutic anticancer vaccines are rarely associated with objective antitumor responses; so, many investigators have focused on progression-free survival (PFS) as a key endpoint for clinical trials. However, it is not clear that PFS is a surrogate for overall survival (OS), and OS may be a more appropriate endpoint because of the effects on long-term memory in the adaptive immune system. Recently, reported vaccine trials were reviewed to determine their primary and secondary endpoints and results. Randomized trials testing sipuleucel-T and prostvac-vf in prostate cancer and ipilimumab and eltrapuldencel-T in melanoma were associated with low objective response rates, no improvement in PFS, but statistically significant improvement in OS. Although compared with PFS, it takes longer to get a final result when OS is the primary endpoint; there is increasing evidence that if long-term memory recognition of tumor-associated antigens is the mechanism of action of an investigational product, then OS may be the only valid clinical endpoint for efficacy.
NeoStem, Inc. , New York, New York.
Robert O
RO
Dillman
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D014020:Tissue Extracts / Q000276:immunology / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000074324:Ipilimumab; C588274:PROSTVAC; D014020:Tissue Extracts; C511774:sipuleucel-T
cancer vaccines; melanoma; overall survival; prostate cancer