If you’re wondering what “castration resistant prostate cancer (CRPC)” is, so are many others. Before I write about the good news, I want to back up and talk about what this means.
Prostate cancer and testosterone
The most newly diagnosed prostate cancer (PCa) cases are composed of slow-growing cell lines. They are typically discovered while still contained in the gland. This is called localized PCa. Treatments for localized PCa include whole gland treatments (radical prostatectomy, radiation, brachytherapy or seed implants, and whole-gland ablation), and partial gland or focal ablation treatments. Survival rates after PCa treatment are very high. However, no treatment comes with a 100% guarantee of cure. If PCa cells are left behind, they may begin to grow again. This is called recurrence, usually signaled by rise in PSA.
The male hormone testosterone plays a major role in fueling the growth of PCa. Therefore, depriving recurrence from access to testosterone tends to halt it – at least for some period. Hormone deprivation consists of various drug protocols, alone or in combination. It has various names:
- Androgen deprivation therapy (ADT)
- Androgen suppression therapy
- Hormone blockade (HB)
- Hormone therapy
- Chemical castration (castration effect using drugs rather than surgical castration of the testes)
Castration resistant prostate cancer (CRPC)
Hormone deprivation is not curative because eventually the cancer overcomes its effect. Then it is called castration resistant prostate cancer (CRPC). When PCa crosses that threshold, it becomes a “Now what do we do?” situation. Doctors have little choice but to monitor CRPC for when it starts to spread (metastasis). Nonmetastatic CRPC (NM-CRPC) is like a ticking time bomb. In almost all cases, it is just a matter of time before metastasis occurs, leaving chemotherapy or immunotherapy as the only strategy. However, NM-CRPC patients with shorter PSA doubling times (the time it takes for PSA to double) are at risk for earlier metastasis and death.
Now there is good news for NM-CRPC patients. In mid-February, 2018, the FDA approved a drug that delays metastasis from occurring. It is called apalutamide (brand name Erleada).
Apalutamide has been under development as a PCa treatment since 2010. It was formulated as a nonsteroidal androgen antagonist, meaning it blocks the receptors of PCa cells from taking up male hormones. After promising results of phase 1and phase 2 clinical studies to determine safety and early effectiveness data, an international team of researchers launched the clinical trial that helped win FDA approval. According to Smith, et al. (2018), “We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less.”[i]
A total of 1207 men with NM-CRPC were enrolled, and randomized on a 2-to-1 basis to receive either apalutamide or placebo (806 apalutamide, 401 placebo). All had been treated for PCa (either surgery or radiation). A noteworthy feature of the study was the defined endpoint (what the FDA agrees is the method to determine the drug’s effect). For this study, the endpoint was “metastasis-free survival, measuring the length of time that tumors did not spread to other parts of the body or that death occurred after starting treatment,” according to FDA Director of Oncology Center of Excellence Richard Pazdur, MD.[ii]
Based on this endpoint, the results were dramatic. The apalutamide group averaged 40.5 months of metastasis-free survival, compared with 16.2 months in the placebo group. Put another way, apalutamide reduced the risk of metastasis or death by 72%.
[i] Smith MR, Saad F, Chowdhury S, Oudard S et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018 Feb 8. doi: 10.1056/NEJMoa1715546. [Epub ahead of print]
[ii] Jason Broderick. “FDA Approves Apalutamide for Nonmetastatic Castration Resistant Prostate Cancer.” OncLive, Feb. 14, 2018. http://www.onclive.com/web-exclusives/fda-approves-apalutamide-for-nonmetastatic-castrationresistant-prostate-cancer