September 18, 2019 – Last night the U.S. Food and Drug Administration (FDA) approved apalutamide (Erleada) for the treatment of metastatic hormone-sensitive (aka, “castration-sensitive”) prostate cancer (mHSPC). Apalutamide has previously received FDA-approval for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC).
PCF funded the initial synthesis of apalutamide at UCLA by chemist Michael Jung, PhD, in collaboration with prostate cancer physician-scientist Charles Sawyers, MD (now at Memorial Sloan Kettering Cancer Center).
mHSPC refers to men whose prostate cancer has spread to areas of the body outside of the prostate itself, and who are responsive to testosterone-lowering agents. This may refer to men who have had prior surgery or radiation and recurred, or men who were initially diagnosed with disease that was already metastatic (outside the prostate). Patients who are “hormone-sensitive” may have previously received androgen deprivation therapy (ADT) for a certain amount of time, but their cancer has not yet developed resistance to ADT.
This approval is based on results from the randomized phase 3 TITAN clinical trial, which was presented at the 2019 American Society of Clinical Oncology (ACSO) Annual Meeting, held in June, and published in the prestigious medical journal, The New England Journal of Medicine.
The TITAN trial, led by PCF-funded investigator Dr. Kim Chi, MD, of the Vancouver Prostate Centre, tested the addition of apalutamide versus placebo, to ADT in 1,052 men with mHSPC. Patients on this trial could have previously received ADT for no more than 6 months for mHSPC or no more than 3 years if used as adjuvant therapy for localized prostate cancer, and were not on ADT at the time of disease progression and trial enrollment. Patients could also have previously received docetaxel chemotherapy for no more than 6 cycles, and could not have progressed on that treatment.
Compared with a placebo, the addition of apalutamide to ADT significantly reduced the risk of death by 33%, and reduced the risk of radiographic disease progression (tumors growing on scans) or death (whichever came first) by 52%. Apalutamide also significantly delayed the average time to PSA progression, use of chemotherapy, and pain progression. Apalutamide was shown to prolong survival of patients with both low and high volume metastatic disease. The treatment combination of apalutamide and ADT was considered tolerable, and quality of life in patients receiving apalutamide was similar to those receiving placebo in addition to ADT. Adverse effects that were higher in patients receiving apalutamide vs placebo included rash (27% vs. 8.5% of patients), hypothyroidism (6.5% vs. 1.1% of patients), and fractures (6.3% vs. 4.6% of patients).
More information on this approval can be found here.