PCF held the 28th Annual Scientific Retreat virtually over 4 days in October and November. Once again, researchers, industry partners, clinicians, patient advocates, and others were able to join from anywhere in the world to discuss the latest findings in prostate cancer research, treatment, and survivorship. PCF’s Dr. Andrea Miyahira has identified the top stories for patients.
PRINCE Trial Shows Promise For Combination of LuPSMA + Pembrolizumab
Shahneen Sandhu, MBBS
Peter MacCallum Cancer Centre, Australia
What this means for patients: LuPSMA is an emerging treatment for advanced prostate cancer that is anticipated to gain FDA approval in the next few months. The results of a recent clinical trial combining LuPSMA with pembrolizumab showed significant promise, with 73% of patients experiencing at least a 50% decline in PSA, and some patients having ongoing complete responses.
177Lu-PSMA-617 (LuPSMA) is a groundbreaking new “seek and destroy” therapy that delivers a radioactive molecule to prostate cancer cells. It significantly improves overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, patients treated with LuPSMA eventually progress, and further optimization is needed. Radiation therapies are thought to cause cancer cells to die in a way that alerts the immune system, and thus may synergize with immunotherapy.
Dr. Sandhu and team led the PRINCE trial to test the combination of LuPSMA with the immunotherapy drug pembrolizumab in 37 patients with mCRPC. Results were encouraging, with 73% of patients seeing their PSA drop by at least 50%. At 24 weeks, 65% of patients had radiographic progression-free survival (rPFS; no worsening of disease on scans). Some patients have had deep and durable responses: For instance, one case was presented in which an 81-year old man experienced a complete response lasting over 60 weeks. Side effects were consistent with those observed for LuPSMA and pembrolizumab alone.
Further studies are needed to define the impact of adding pembrolizumab to LuPSMA on rPFS and overall survival.
Harnessing Immune Cells to Kill Prostate Cancer
Oliver Sartor, MD
What this means for patients: Bi-specific antibodies are a promising experimental class of treatments for advanced prostate cancer that leverage the body’s immune system to kill tumor cells. Early-phase clinical trials show efficacy for several different bi-specific antibodies. Future studies will test new agents and address mechanisms of resistance.
There is a crucial need for effective treatments for metastatic castration-resistant prostate cancer (mCRPC). One option involves immunotherapy, helping the body’s T cells to recognize, bind to, and kill cancer cells. Bi-specific antibodies are specially-designed proteins that have two (hence the “bi”) parts and can bind to T-cells and tumor cells simultaneously. When these treatments are infused into the patient, they find their way to the tumor, bringing the T cells with them.
As one example, AMG 160 is a bi-specific antibody that binds to prostate-specific membrane antigen (PSMA) with one of its “arms” and T-cells with the other. In a phase 1 study, nearly 70% of patients had a reduction in PSA. Certain precautions are taken to lessen side effects associated with stimulating the immune system. AMG 160 is being tested in combination with other medicines, and a number of other therapies in this class are in early-stage clinical development for the treatment of prostate cancer.
Using VA Prostate Cancer Data to Improve Clinical Trials
Tito Fojo, MD, PhD
Columbia University and the James J. Peters VAMC
What this means for patients: Dr. Fojo and colleagues have developed a new method called “g” to calculate tumor growth rate. g strongly predicts overall survival, the current “gold standard” outcome in clinical trials. g may eventually be used in several ways to accelerate trials and the development of new treatments.
Currently, the criteria for measuring disease response versus progression in prostate cancer is based on changes in tumors on scans. PSA responses are also used, but are not considered valid by the FDA to determine the efficacy of new treatments. Dr. Fojo and colleagues have developed a novel method to calculate tumor regression and growth that is more accurate and informative than standard methods.
This new approach, called “g,” is calculated from PSA levels over time. The research team found that g strongly predicts overall survival, and thus may act as a “surrogate biomarker” for making treatment decisions and evaluating the efficacy of a new treatment. (In other words, g may provide information earlier about how well a treatment works, rather than waiting many years for survival data.) They also evaluated the use of g as a marker in a large study of Veterans who were switched from abiraterone to enzalutamide or vice versa. How to identify which patients should remain on a therapy vs. switch to another is an important question.
Using existing data, g can be used to reduce the size of or even eliminate control arms. g could also be used to inform decisions about new treatments under development, and make decisions with small numbers of patients, including those with rare cancers or rare mutations. The FDA has requested further studies to evaluate g for use in clinical trials.
Prostate Cancer Disparities: What We Know, and What We Can Do
Brandon Mahal, MD
University of Miami
What this means for patients: Prostate cancer disparities result in large part from unequal access to care. Additional research on biology and genetic factors remains to be done. Solutions must be multi-pronged, including: increasing access to insurance and clinical trials, and actively engaging diverse communities.
African Americans are over 75% more likely than Caucasians to be diagnosed with prostate cancer, and more than twice as likely to die from it. We know that genetics plays some role, but the impact of social and economic inequalities is better defined. One such factor is medical insurance: Mahal and colleagues have reported that among uninsured men with prostate cancer, Black men were much more likely to go untreated (28%) vs. Caucasian men (16%). Knowing about gene mutations in a tumor can help save lives, but research studies include relatively fewer people of non-European ancestry. Moreover, Black men tend to get this type of tumor testing later in their treatment course.
Solutions to disparities requires research in diverse populations, and outreach programs to bring care delivery and cutting-edge science to diverse communities. Patients and communities must be engaged as research partners rather than subjects. These approaches should incorporate transparency, education, acknowledgment of the history of racism, and a diverse oncology workforce.
Read Part 1, Research on Survivorship and Lifestyle here.