Over the course of prostate cancer progression, there can come a time during which the cancer is progressing, but there are no treatments known to improve survival. One of these “empty spaces” is when men who are being treated with androgen deprivation therapy (ADT) see their PSA levels begin to rise (indicating the cancer has become resistant to ADT and is starting to grow again), but no metastases are visible yet on scans. This clinical state is termed “non-metastatic castration-resistant prostate cancer” (non-metastatic CRPC). Many of these men will ultimately go on to develop metastases and lethal prostate cancer. Until today, there were no other options and these men often just continued to receive ADT despite its diminishing benefit.
At the 2018 ASCO Genitourinary Cancers Symposium, held February 8-10 in San Francisco, California, results from two randomized phase 3 clinical trials, SPARTAN and PROSPER, may have filled this empty space. Enzalutmide (Xtandi) and Apalutamide (Erleada; ARN-509) are two highly similar hormonal treatments that when added to ADT (or whatever treatments were already being used) were found to significantly delay the onset of metastases and several other measures of cancer progression in men with non-metastatic CRPC.
The PROSPER trial, led by Prostate Cancer Foundation (PCF)-funded investigator Maha Hussain, MD (Northwestern University), tested the addition of enzalutamide vs. placebo in 1,401 non-metastatic CRPC patients who were continuing to receive ADT despite a rapidly rising PSA. Enzalutamide was found to delay the time to metastatic disease by 22 months on average, compared with placebo.
The SPARTAN trial, led by PCF-funded investigator Eric Small, MD (University of California, San Francisco), tested the addition of apalutamide vs. placebo in 1,207 non-metastatic CRPC patients with rapidly rising PSA, in addition to whatever treatment the men were already receiving (mostly ADT). Apalutamide was found to delay the time to metastatic disease by over 24 months on average. The full results from the SPARTAN study were simultaneously published in the New England Journal of Medicine.
This could be amazing news for patients with CRPC.
“We don’t yet know if either apalutamide or enzalutamide increases the survival duration in these patients, although early indication is in that they will,” said Philip Kantoff, MD, PCF-funded investigator and Chairman of the Department of Medicine at Memorial Sloan Kettering Cancer Center, who led the discussion on the trials at the Symposium. “Patients do need to be aware that these treatments when used early, can cause greater treatment exposure and greater chance for toxicity including a small chance of unexplained death. Nonetheless these trials may change practice patterns in a major way and provide treatment opportunities for men with no current effective therapies.”
These two treatments are highly similar oral medications, differing by only a single atom. PCF previously funded the synthesis of these treatments at UCLA by chemist Michael Jung, PhD, in collaboration with prostate cancer physician-scientist Charles Sawyers, MD (now at Memorial Sloan Kettering Cancer Center). They have since been separately licensed and developed by different pharmaceutical companies.
Apalutamide is a new medicine, whereas enzalutamide is already FDA-approved for metastatic CRPC. Both of these treatments are now under review by the FDA for use in non-metastatic CRPC, and decisions – and the change in practice that will accompany an FDA approval — are expected very soon.