Understanding Progression

In clinical trials:

Men with mCSPC who received ADT alone were at elevated risk of disease progression1-5

In men who received ADT alone for metastatic castration-sensitive prostate cancer (mCSPC), the median time to the development of castration resistance was < YEAR in a clinical trial*1

For men with low-volume disease2

22.7

months

For men with high-volume disease2

8.6

months

The median overall survival of men with mCSPC who were treated with ADT alone was YEARS in clinical trials‡2-6

*Time to development of castration-resistant prostate cancer was assessed in a randomized clinical trial of 790 patients with mCSPC. Time to castration-resistant prostate cancer was defined as the time until documented clinical or serologic progression with a testosterone level <50 ng/dL (or source documentation of medical castration or surgical castration).2

In this clinical trial, high-volume mCSPC was defined as the presence of visceral metastases and/or ≥4 bone lesions with at least 1 lesion outside of the vertebral column and/or pelvis.1

Based on patients in the control arms of 5 randomized clinical trials.2-6

ADT = androgen deprivation therapy; TITAN = Targeted Investigational Treatment Analysis of Novel Antiandrogen.

References

1. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746.

2. Kyriakopoulos CE, Chen YH, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36(11):1080-1087.

3. Gravis G, Boher JM, Joly F, et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol. 2016;70(2):256-262.

4. Fizazi K, Tran N, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20(5):686-700.

5. James ND, de Bono JS, Spears MR, et al; STAMPEDE Investigators. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338-351.

6. James ND, Spears MR, Clarke NW, et al. Survival with newly diagnosed metastatic prostate cancer in the “docetaxel era”: data from 917 patients in the control arm of the STAMPEDE trial (MRC PR08, CRUK/06/019). Eur Urol. 2015;67(6):1028-1038.

 

Certain men with non-metastatic CRPC are at risk of developing metastases1

10% to 20%
of men diagnosed with prostate cancer are estimated to develop CRPC within 5 YEARS of follow-up2

Data from 331 subjects in the placebo group of a randomized controlled trial of an investigational agent were analyzed to evaluate the relationship between disease and patient characteristics with time to first bone metastases in men with prostate cancer, rising PSA despite ADT, and no radiographic evidence of metastases.3

After 2 years:

46% had developed at least
1 bone metastasis

In men with non-metastatic CRPC, a faster PSA doubling time (PSADT) has been linked to shorter time to metastasis1

When compared with patients who experienced a PSADT ≥10 months, those with a PSADT <10 months had*4:

12x greater risk of developing
a bone metastasis

*Retrospective study of 347 patients with CRPC from a cohort of 9547 patients who underwent treatment for prostate cancer, using the Center for Prostate Disease Research database.

Androgen receptor (AR) signaling remains relevant in CRPC5

  • The goal of continuous ADT is to maintain castrate levels of serum testosterone (≤50 ng/dL)6
  • However, several resistance mechanisms, including AR overexpression, can lead to CRPC7

ADT = androgen deprivation therapy; CRPC = castration-resistant prostate cancer; PSA = prostate-specific antigen; SPARTAN = Selective Prostate Androgen Receptor Targeting with ARN-509.

References

1. Howard LE, Moreira D, De Hoedt A, et al. Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int. 2017;120(5B):E80-E86.

2. Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011;65(11):1180-1192.

3. Smith MR, Cook R, Lee KA, Nelson JB. Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer. Cancer. 2011;117(10):2077-2085.

4. Metwalli AR, Rosner IL, Cullen J, et al. Elevated alkaline phosphatase velocity strongly predicts overall survival and the risk of bone metastases in castrate-resistant prostate cancer. Urol Oncol. 2014;32(6):761-768.

5. Mitsiades N. A road map to comprehensive androgen receptor axis targeting for castration-resistant prostate cancer. Cancer Res. 2013;73(15):4599-4605.

6. Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34(12):1402-1418.

7. Kahn B, Collazo J, Kyprianou N. Androgen receptor as a driver of therapeutic resistance in advanced prostate cancer. Int J Biol Sci. 2014;10(6):588-595.