Therapeutic sequencing improves outcomes for patients with progressive mCRPC

Nov. 20, 2020

Despite advances in the management of prostate cancer, it remains the second most common cause of cancer-related deaths among men. In 2020, approximately 192,000 new prostate cancer cases will be diagnosed and nearly 33,000 men will die of prostate cancer this year.

While most forms of prostate cancer run an indolent course, metastatic castration-resistant prostate cancer (mCRPC) has an aggressive outlook and accounts for the majority of prostate cancer deaths.

In the modern era, several promising treatment options have emerged for the management of mCRPC, including androgen receptor inhibitors (ARIs) such as abiraterone and enzalutamide; chemotherapy agents such as docetaxel, cabazitaxel and carboplatin; and radioactive isotope agents such as radium-223. Associated with this broad treatment armamentarium, however, is ambiguity surrounding the optimal sequencing of these agents that will best service this vulnerable patient population.

In 2019, in the open-label CARD trial published in The New England Journal of Medicine, researchers evaluated the efficacy of cabazitaxel versus an ARI (either abiraterone or enzalutamide) among a group of patients with mCRPC previously treated with docetaxel and an ARI who demonstrated disease progression. The study supported that treatment with cabazitaxel was superior to switching to an alternative ARI with respect to progression-free survival and overall survival.

In a separate study, published in The Lancet Oncology in 2019, the addition of carboplatin to cabazitaxel versus cabazitaxel alone improved progression-free survival from a median 4.5 months to 7.3 months among patients with mCRPC experiencing disease progression on ARIs.

Optimal treatment sequencing for mCRPC

Given the promise demonstrated by combination chemotherapy for patients with mCRPC, Eugene D. Kwon, M.D., and a team of Urology researchers at Mayo Clinic in Rochester, Minnesota, sought to investigate the long-term oncologic outcomes of three different chemotherapy regimens in patients who had experienced disease progression after treatment with a novel ARI.

"We are very interested in finding the best way to sequence systemic treatment for these patients who have aggressive disease," says Paras H. Shah, M.D., a urologic oncologist and one of the study authors. Study results were published in The Prostate in 2020.

Dr. Kwon and fellow researchers performed a review of 150 patients treated with one of the following regimens after progression on either enzalutamide or abiraterone:

  • Docetaxel alone (90 patients)
  • Docetaxel plus carboplatin (33 patients)
  • Cabazitaxel alone (27 patients)

Researchers observed that the addition of carboplatin to docetaxel improved the likelihood of favorable clinical response compared with systemic monotherapy. An objective treatment response, defined as a reduction in PSA of 50% or more from the pre-treatment level, was observed among 63% of patients receiving docetaxel plus carboplatin versus in only 40% and 37% of patients receiving either docetaxel or cabazitaxel, respectively ― thus corresponding to 2.6 greater odds of treatment response among those receiving combination therapy.

Moreover, significant improvement in 30-month overall survival rates was noted among patients receiving the combination docetaxel and carboplatin (70.7%) compared with patients who received docetaxel alone (38.9%) or cabazitaxel alone (30.3%).

Dr. Kwon summarizes the study by saying, "These results lend support to the use of a combination chemotherapy regimen consisting of carboplatin and docetaxel in patients with progressive mCRPC disease who were previously treated with ARIs such as abiraterone or enzalutamide. We are enthusiastic about our findings, as they present another step in improving the strategy of therapeutic sequencing for these patients. Our hope is that these study findings translate to significant improvements in patient longevity."

For more information

de Wit R, et al. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. The New England Journal of Medicine. 2019;381:2506.

Corn PG, et al. Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: A randomised, open-label, phase 1-2 trial. The Lancet Oncology. 2019;20:1432.

Ahmed ME, et al. Adding carboplatin to chemotherapy regimens for metastatic castrate‐resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes. The Prostate. 2020;80:1216.