Clinicians Want Efficacy Measures
That the treatment doesn’t drop patients’ PSA levels or improve time to progression are more pressing considerations, as they relate to the value of the treatment, rather than the cost, clinicians observed in interviews.
"The lack of PSA response, or more specifically, the lack of correlation of PSA changes, makes use of [sipuleucel-T] problematic, as it is unclear from the trial data how to measure treatment efficacy and when to initiate new treatments," said Dr. Edouard J. Trabulsi, a urologist at Thomas Jefferson University and director of the multidisciplinary genitourinary cancer clinic at the Kimmel Cancer Center, both in Philadelphia.
Although the treatment is indicated for asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer, the bottom line for Dr. Evan Yu, an oncologist at the University of Washington, Seattle, "is that we don’t know who will benefit from it. We know that the population that received Provenge lived longer in the IMPACT trial, but the fact that there was no improvement in time to progression, and the survival curves didn’t separate until 6 months, tells us that a reasonable portion of patients may not benefit from it."
That said, Dr. Yu added that "there clearly are patients who will receive significant benefit from sipuleucel. We just aren’t sure who those patients are. My best guess is that it may be patients with low-volume disease and slow progression, but it is not always easy to identify this patient population. As a result, predictive and response biomarkers are needed, and Dendreon is doing research in this area."
Although it is clear that clinicians in practice should probably be more selective than the IMPACT population, "we have no data or guidelines to aid us in this selection process," he said.
Indication Limits Likely Patients
The reality, for now, is that sipuleucel-T "is indicated for a very narrow space in prostate cancer – the minimally symptomatic metastatic hormone-refractory patient prior to chemo – and likely will not be expanded widely to the entire advanced prostate cancer spectrum in the absence of additional clinical trial data," said Dr. Trabulsi.
In addition to the relatively narrow patient population for sipuleucel-T, the recent FDA approval of Johnson & Johnson’s abiraterone acetate (Zytiga), an oral inhibitor of testosterone synthesis, in combination with prednisone and the anticipated approval of Medivation’s oral testosterone- and dihydrotestosterone-blocking MVD3100 may have taken some of the wind out of sipuleucel-T’s sails, he noted.
Still, the denouement of the sipuleucel-T story should not be scripted by analysts or angry investors. At the end of the day, the FDA approval of the cancer "vaccine" does represent a milestone in the history of oncology, Dr Trabulsi said.
"[Sipuleucel-T] is very important as it shows a survival benefit and confirms the principle of immunomodulation being effective for prostate cancer," he said. "It also is illustrative of the new process for approval we likely will be seeing for expensive new treatments, as its use off label is severely restricted from earlier prostate cancer populations, which is unprecedented for FDA-approved drugs."
Dr. Kantoff has served as a consultant/adviser for Amgen and has received research funding from Sanofi-Aventis. Dr. Yu has received research funding support from OncoGenex Technologies and is a member of the U.S. Dept. of Defense–supported Prostate Cancer Clinical Trials Consortium. Dr. Trabulsi disclosed no relevant financial relationships.