Cancer Treatment Today

ZYTIGA in combination with prednisone was initially FDA indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) who have received prior chemotherapy containing docetaxel.  However, there are now two studies that argue for combining Zytiga with ADT even in patients who are not metastatic and had not beend efinitively treated with a prostatectomy.
The STAMPEDE trial began in 2005 and is the largest randomized clinical trial of treatments for prostate cancer. This ongoing study has a multistage, multi-arm design to allow adaption and addition of new therapies. An abiraterone comparison arm was opened in 2011 and closed January 2014. Enrolled patients included those with high-risk locally advanced or metastatic prostate cancer that was newly diagnosed or relapsed after radical prostatectomy or radiation therapy and who were starting ADT. In the abiraterone group, OS was improved by 37% compared with the standard-of-care group (hazard ratio [HR] 0.63, 95% CI [0.52, 0.76]; p = 0.00000115).

The LATITUDE trial randomly assigned 1,199 patients with newly diagnosed, high-risk, hormone-sensitive metastatic prostate cancer to receive ADT plus placebo (602 patients) or ADT plus abiraterone and prednisone (597 patients). High-risk was defined as two of three factors including a Gleason score of at least 8, thus, this trial did nto icnldue locallya dvanced non-metastatic patients. The median OS with ADT and placebo was 34.7 months, but was not yet reached in the abiraterone group (HR 0.62, 95% CI [0.51, 0.76]; p < 0.0001). The OS rate at 3 years was 66% with abiraterone and prednisone, and 49% without. rPFS improved with abiraterone as well. The median rPFS in the control group was 14.8 months compared with 33.0 months with abiraterone (HR 0.47, 95% CI [0.39, 0.55]; p < 0.0001).

In conclusion, Zytiga with ADT may be more effectivce than ADT alone, but almost all of the evidence, except for some patietns in the STAMOPEDE trial, were metastatic. The Latitude trial is still being digested, and it has not been adopted by guidelines and not standard of care at this time. In addition, there is no strong evidence supporting this regimen in a non-metastatic setting.

Taplin ME, Montgomery RB, Logothetis C, et al. Effect of neoadjuvant abiraterone acetate (AA) plus leuprolide acetate (LHRHa) on PSA, pathological complete response (pCR), and near pCR in localized high-risk prostate cancer (LHRPC): Results of a randomized phase II study. J Clin Oncol. 2012;30:(suppl; abstr 4521).

Mary-Ellen Taplin, Bruce Montgomery, Christopher J. Logothetis, Glenn J. Bubley, Jerome P. Richie, Bruce L. Dalkin, Intense Androgen-Deprivation Therapy With Abiraterone Acetate Plus Leuprolide Acetate in Patients With Localized High-Risk Prostate Cancer: Results of a Randomized Phase II Neoadjuvant Study Journal of Clinical Oncology 32, no. 33 (November 2014) 3705-3715.

Efstathiou E, Davis JW, Titus MA, et al. Neoadjuvant enzalutamide (ENZA) and abiraterone acetate (AA) plus leuprolide acetate (LHRHa) versus AA+ LHRHa in localized high-risk prostate cancer (LHRPC). J Clin Oncol. 2016; 34 (suppl; abstr 5002).

NCCN, PROS-F 2017

Nicholas D. James net al, Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med 2017; 377:338-351July 27, 2017

Karim Fizazi, M.D., Ph.D., NamPhuong Tran, M.D., Luis Fein, M.D., Nobuaki Matsubara, M.D., Alfredo Rodriguez-Antolin, M.D., Ph.D., Boris Y. Alekseev, M.D., Mustafa Özgüroğlu, M.D., Dingwei Ye, M.D., Susan Feyerabend, M.D., Andrew Protheroe, M.D., Ph.D., Peter De Porre, M.D., Thian Kheoh, Ph.D., Youn C. Park, Ph.D., Mary B. Todd, D.O., and Kim N. Chi, M.D., for the LATITUDE Investigators*Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2017; 377:352-360July 27, 2017