“Advancements in immunotherapy in the field of prostate cancer have been slow ever since the FDA approval of sipuleucel-T (Provenge) several years ago.
” ‘It’s an exceptionally challenging area. After the success of sipuleucel-T, there have been combinatorial approaches using radiopharmaceuticals, such as radium-223, the checkpoint inhibitor ipilimumab (Yervoy), as well as some chemotherapy regimens,’ says Susan F. Slovin, MD, PhD.
“In an interview with OncLive at the 2017 Interdisciplinary Prostate Cancer Congress, Slovin, a medical oncologist at Memorial Sloan Kettering Cancer Center, offered her expert insight on the current state of immunotherapy in prostate cancer.”
“The surface has only been scratched in the investigation of radiation and immunotherapy in combination for the treatment of patients with prostate cancer, says Steven Finkelstein, MD, of 21st Century Oncology.
“ ‘There is so much undiscovered territory with respect to this research. The fact there that are only a few clinical trails now of any significance in this area means that we need to do more work,’ says Finkelstein, a Scottsdale board certified radiation oncologist, adjunct associate professor at Translational Genomic Research Institute, and executive director of the Arizona Cancer Research Alliance. ‘I’ve spent a career working on this topic, and only now, after 20 years, are we starting to make progress.’
“While progress has been slow, the outlook is bright for the use of immunotherapy and radiation together in prostate cancer, says Finkelstein. He is currently working on a multicenter trial, which is investigating the effects of radiation therapy to augment anti-tumor responses from immunotherapy with sipuleucel-T (Provenge).”
“Judd W. Moul, MD, urologic oncologist, Duke Medicine, discusses the impact of immunotherapy in prostate cancer.
“Urologists are more aware of immunotherapy than most cancer specialists, says Moul. He and his colleagues have been working with Bacillus Calmette-Guérin (BCG) in bladder cancer for many years, as well as interleukin 2 in kidney cancer.
“Sipuleucel-T (Provenge), commercialized by Dendreon, has also made quite a difference in prostate cancer, adds Moul. Unfortunately, this drug has never become widespread because of its perceived complexity of administration, as well as cost.
“Preliminary results from the phase II STAND trial have demonstrated a robust immune response with sipuleucel-T (Provenge) that continues 2 years after completing treatment in men with biochemically recurrent prostate cancer. The findings, along with data from an ongoing phase IV registry related to increasing enrollment of African Americans in prostate cancer trials, are being presented at the 2015 Genitourinary Cancers Symposium, held February 26 to 28 in Orlando…
“The STAND study (Abstract 171) is a randomized, phase II trial that consisted of two patient study groups. One group completed sipuleucel-T 2 weeks before initiation of androgen-deprivation therapy, and the second received the drug 3 months after the start of androgen-deprivation therapy. Preliminary results from STAND indicate that immune responses were observed in both study arms and suggest there may be a greater cellular immune response in patients who received sipuleucel-T prior to androgen-deprivation therapy. Humoral immune responses were observed and similar between both treatment arms.
“ ‘It is very encouraging to observe that [sipuleucel-T] provides an immune response in men with biochemical-recurrent prostate cancer long after the course of androgen deprivation therapy has ended,’ said Neal Shore, MD, Medical Director at the Carolina Urologic Research Center. ‘This study may also provide guidance on the optimal sequencing of immunotherapy and androgen-deprivation therapy in biochemical-recurrent prostate cancer.’ ”
The gist: The drug sipuleucel-T (Provenge) may be no better than watchful waiting and standard androgen deprivation therapy for certain prostate cancer patients. That was the conclusion of the German Institute for Quality and Efficiency in Health Care (IQWiG). The IQWiG analyzed data on men with metastatic prostate cancer who had few or no symptoms and did not yet need chemotherapy.
“Sipuleucel-T (trade name Provenge) has been approved since September 2014 for men with metastatic prostate cancer who have few or no symptoms and do not yet require chemotherapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether the drug offers patients an added benefit over one of the appropriate comparator therapies.
“According to the findings, an added benefit is not proven: The data on mortality were not evaluable because differences between the treatment groups might have been caused by the circumstances of the subsequent therapies. At the same time, certain side effects such as fever occur more frequently.
“Treatment with sipuleucel-T aims to stimulate the immune system to kill cancer cells. Immune cells are extracted from the patient’s blood and treated with a protein in a laboratory. These treated cells are then injected back into the patient’s blood where they are supposed to better recognize cancer cells and stimulate the immune system to fight the prostate cancer.
“Sipuleucel-T is an option for patients whose cancer has already formed metastases and can also no longer be influenced by blocking the hormone testosterone (hormone refractory).”
“Dendreon Corporation (NASDAQ: DNDN) today announced the presentation of preliminary data from a long-term analysis of the Phase II STAND study demonstrating that tumor-specific T-cell responses appear to be enhanced and sustained when PROVENGE^® (sipuleucel-T) is given after androgen deprivation therapy (ADT) in patients with biochemically-recurrent prostate cancer (BRPC) at high risk for metastases. These data will be presented at the 29^th Annual European Association of Urology (EAU) Congress taking place from April 11-15, 2014 in Stockholm, Sweden.”
Editor’s note: This story is about a study that demonstrated positive patient responses when the cancer vaccine Provenge was given as a prostate cancer treatment after patients were first treated with androgen deprivation therapy (ADT). The study focused on patients with biochemically-recurrent prostate cancer (BRPC) at high risk for metastasis.
Patel JC, Maughan BL, Agarwal AM, Batten JA, et al. Prostate Cancer. May 8, 2013.
“Androgen deprivation therapy (ADT) with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC) and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR) signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700), and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials.”
Advanced prostate cancer patients used to be treated with palliative chemotherapy that did not improve survival. But in the past decade, researchers have introduced several new therapies for castration-resistant prostate cancer (CRPC) and related complications. These drugs include cabazitaxel (Jevtana), abiraterone acetate (Zytiga), enzalutamide (Xtandi), sipuleucel-T (Provenge), radium-223, and denosumab (Xgeva or Prolia). Two researchers recently performed a cost-benefit analysis on these new therapies. They say that costs will come down as treatment strategies—including precisely timed combinations of drugs—are refined to minimize progression and side effects.
In April of 2010, the Food and Drug Administration (FDA) approved the first immunotherapy for prostate cancer. Sipuleucel-T (Provenge), an autologous active cellular immunotherapy (a cancer vaccine), was approved for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T was also the first active cellular immunotherapy approved by the FDA and, at the time of approval, only the second approved drug for mCRPC patients. Prior to approval, the only other option for these patients was the chemotherapy docetaxel. Continue reading…