Erleada Treatment for Men With Prostate Cancer and a Rising PSA

Cancer Connect

by Dr. C.H. Weaver M.D. updated 1/2019

The U.S. Food and Drug Administration (FDA) has approved Erleada (Apalutamide) for the treatment of non-metastatic castration-resistant prostate cancer (CRPC), (1) and new data from the TITAN clinical trial have also shown that Erleada will benefit men with metastatic castration-sensitive prostate cancer (mCSPC).(2)

About Erleada ™

Erleada™ is an androgen receptor (AR) inhibitor that works by binding directly to the ligand-binding domain of the AR. Erleada™ inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription.

Erleada in Castration-Sensitive Prostate Cancer

The phase 3 TITAN clinical trial evaluated Erleada® plus androgen deprivation therapy (ADT) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). mCSPC refers to prostate cancer that still has spread away from the prostate gland to other parts of the body but still responds to ADT. The trial directly compared ADT with or without Erleada. An Independent Data Monitoring Committee recommended halting the trial because Erleada significantly delayed cancer progression and prolonged survival and initial results were presented at the June 2019 American Society of Clinical Oncology Annual Meeting. (2)

525 men were treated with Erleada 240 mg daily plus continuous ADT in 28-day cycles and compared to 527 men treated with continuous ADT alone.

The addition of Erleada to ADT conferred a 52% reduction in risk for death or radiographic progression. At 2 years, results showed an absolute 20 percentage point difference in the rate of cancer progression in favor of Erleada. At 2 years the overall survival rate were was 82% for Erleada compared to 74% for ADT alone.

Erleada in Castration-Resistant Prostate Cancer

For men who are being treated with androgen deprivation therapy (ADT) and see their prostate specific antigen (PSA) levels begin to increase Erleada represents an effective new treatment option. Erleada is the first FDA-approved treatment for non-metastatic CRPC.

Prostate cancer is the second most common cancer in men worldwide. More than 164,000 men in the United States are estimated to be newly diagnosed with prostate cancer in 2018. (3,4)Castration-resistant prostate cancer refers to the subset of men whose prostate cancer progresses despite castration levels of testosterone. (5) Non-metastatic CRPC means there is no clinically detectable evidence of the cancer spreading to other parts of the body (metastases), and there is a rising prostate-specific antigen (PSA) level.(6) Many men with non-metastatic CRPC and a rapidly rising PSA level go on to develop metastatic CRPC.(7) The relative 5-year survival rate for patients with distant stage prostate cancer is 30 percent and therapies that can delay the onset of metastasis in these patients is needed.

The FDA approval is based the results of a pivotal clinical trial presented last week at the 2018 ASCO Genitourinary Cancers Symposium. The trial evaluated 1,207 non-metastatic CRPC patients with a rapidly rising PSA (PSA doubling time of 10 months or less) and no evidence of distant metastatic cancer. Half the individuals received Erleada in addition to whatever treatment they were already receiving (mostly ADT) and were compared to those not offered Erleada.

Erleada treated patients experienced a delay in the time to metastatic disease of 40.5 months compared to only 16.2 months for those not receiving the medication. This represents a 72% reduction in risk of metastasis or death.(1)

References:

  1. https://www.pcf.org/news/fda-approves-apalutamide-erleada/?utm_source=pcflist&utm_medium=email&utm_campaign=20180214fda
  2. Chi KN, et al. Abstract 5006. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
  3. American Cancer Society. Cancer Facts & Figures 2018. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-….
  4. European Commission. Epidemiology of Prostate Cancer in Europe. https://ec.europa.eu/jrc/en/publication/epidemiology-prostate-cancer-europe.
  5. Urology Care Foundation. Advanced Prostate Cancer Patient Guide. urologyhealth.org/educational-materials.
  6. Luo J, Beer T, Graff J. Treatment of Non-metastatic Castration Resistant Prostate Cancer. Oncology. April 2016, 30(4):336-344.
  7. Smith MR, Kabbinavar F, Saad F, Hussain A et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol 2005; 23: 2918–2925.
Epidemiology of prostate cancer in Europe - EU Science Hub - European Commission
Epidemiology of prostate cancer in Europe - EU Science Hub - European Commission

- Reliable information on the burden and outcome of cancer in a population are provided by population-based cancer registries (CR). CR uses multiple sources of information (hospital discharge notes, pathology reports, death certificates, etc.) to supply complete and solid data on cancer’s frequency and survival in defined populations. European CR, including those of the 28 member states of the European Union, are embraced in the European Network of Cancer Registries, a scientific association which provides recommendations on the classifications and procedures that CR should follow. Since 2013 ENCR is supported by the European Commission and the ENCR Secretariat is hosted at the Joint Research Centre in Ispra, Italy. ENCR-JRC has just launched a call for data, asking to about 150 regional and national European CR to contribute to its database hosted at the JRC. The CR will be able to upload the data via a web portal devised at JRC. Such a portal streamlines data entry and allows CR to participate in multiple studies avoiding duplicate submissions. In the European Union, prostate cancer is ranked first among the most frequently diagnosed cancer among men, with around 345,000 new cases estimated in 2012. Prostate cancer accounted for 24 per cent of all new cancers in the same year. For 2015 the estimated number of new prostate cancer cases is about 365,000. Within the European Union there is a huge variability in incidence rates, from Sweden (age-adjusted rate on the European standard population, ASR 175) to Greece (ASR 34). Although age standardized rates (ASRs) are still increasing in many countries, in some others they have started to flatten (e.g. USA, Denmark, Finland, Sweden, etc.). In the EU, about 72,000 deaths (10 per cent of the total cancer deaths) were estimated in 2012 and almost 77,000 are expected in 2015. ASR mortality rates vary across countries although to a lesser extent than incidence, from Lithuania (ASR mortality 36) to Malta (ASR 14). ASRs for prostate cancer mortality are decreasing in many countries. As regards five-year prevalence (number of people who have had a cancer diagnosis in the last 5 years), about 1,300,000 citizens of the European Union are estimated to have had a prostate cancer diagnosis in the last five years. They represent a burden for health services in terms of requests and needs for follow-ups. Concerning survival, the Eurocare project has compared cancer survival data among European countries since 1989. The on-going project – Eurocare 6 – has been launched in collaboration with ENCR-JRC through the ENCR-JRC web portal. The most recent data of the Eurocare project, on 5-year relative survival for cancers diagnosed in 2003-2007, show that prostate cancer ranked fourth in Europe among the cancers with the best prognosis with a 5-year relative survival of 83%. Survival varied from 88% in Southern and Central European countries to 76% in Eastern ones. Moreover, in all the European countries survival has increased over time with the highest improvement observed in the Eastern countries. (De Angelis et al. Lancet 2014) The epidemiology of prostate cancer has been strongly modified by the introduction and the widespread use of the Prostate Specific Antigen testing (PSA) and of the following diagnostic procedures (biopsy). PSA is a blood test highly sensitive to detecting a growth in the prostate tissue. In the USA, after its introduction in the late 80s, incidence rates had doubled in few years. A smaller but similar increase in prostate cancer incidence succeeded the introduction of PSA testing also in the other, mainly western-type, countries. PSA has been tested to evaluate its possible role as a screening test in healthy asymptomatic men. Unfortunately, although it turned effective in reducing prostate specific mortality, the relevant over diagnosis, – that is the diagnosis of indolent tumours which once diagnosed are treated as deadly cancers, – and the severe side effects of treatments, advised against the introduction of PSA as a screening programme. Any evaluation of the changes that have occurred in Europe in the last 15-20 years in the epidemiology of prostate cancer cannot be conducted without considering the role of PSA testing and the related amount of over diagnosis.

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