Non-metastatic castrate-resistant prostate cancer (nmCRPC) is a clinical state in which a patient on androgen-deprivation therapy (ADT) has a rising PSA but there are no radiological findings of metastases on CT or bone scan. Management of nmCRPC is evolving quickly, but it is a field in which there have been recent drug approvals amid a strong and growing interest in keeping patients metastasis-free for as long as possible. About 10-20% of prostate cancer cases are castrate-resistant, but nearly 16% of those castrate-resistant patients have no evidence of metastatic disease at the time their castrate-resistance is diagnosed.
Not all nmCRPC disease is the same. For some patients, observation is a viable option; for other patients—especially those with a PSA doubling time of less than or equal to 10 months—randomized Phase III clinical trials have shown a benefit and an increase in metastasis-free survival with the use of Xtandi (enzalutamide) or Erleada (apalutamide). New imaging techniques on the horizon may also be very helpful in assessing nmCRPC patients.
In February 2018, the FDA approved Erleada (apalutamide) for nmCRPC patients and was the first such FDA-approved treatment for this subset of patients—i.e. those who are no longer responding to ADT but who have no radiological evidence of metastasis. The Erleada (apalutamide) approval followed the release of the results of SPARTAN, a randomized clinical trial of 1,207 patients in which patients received either Erleada (apalutamide) or placebo, discussed at the American Society of Clinical Oncology Genitourinary (ASCO GU) Meeting in February of this year. All of the patients who were enrolled also received hormone therapy. The exciting results showed that the median metastasis-free survival for patients in the Erleada (apalutamide) arm was 40.5 months versus 16.2 months for the placebo group. Both applications received priority review from the FDA due to the exciting results with clear benefit for nmCRPC patients.
The results of another trial known as the PROSPER Trial were also first presented at the 2018 ASCO GU Meeting. In PROSPER, with 1,401 participants, men with nonmetastatic castrate-resistant prostate cancer (nmCRPC) were given either Xtandi (enzalutamide) or placebo; these were men in whom the PSA doubling time was 10 months or less, but, again, there was no evidence of disease seen by CT or bone scan or by MRI. Those nmCRPC patients receiving Xtandi (enzalutamide) had delayed time to metastatic disease or death (whichever occurred first) by a median of 21.9 months, versus placebo (36.6 months compared to 14.7 months), signifying a 71% reduction of the risk for metastasis or death. Another result: Xtandi (enzalutamide) delayed the time until men needed additional cancer treatment, compared to placebo (a median of 39.6 months compared to 17.7 months). On July 13, 2018 the FDA approved Xtandi (enzalutamide) for the treatment of nmCRPC patients.
This means that men with nonmetastatic castrate-resistant prostate cancer now have two choices that they did not have before, when they would simply be continued on ADT. We still do not know, however, if the added Xtandi (enzalutamide) or Erleada (apalutamide) will increase overall survival for these patients.
[This article deals only with nonmetastatic CRPC. There have also been various trials conducted in the metastatic space, and there are other trials currently underway or planned involving anti-androgens such as Zytiga (abiraterone), including some in combinations with other types of therapy, dealing with metastatic disease (mCRPC patients). One of the trials looking at the metastatic disease space is the PEACE1 Trial, which is looking at the benefit of Taxotere (docetaxel) plus ADT, with or without Zytiga (abiraterone) and prednisone, and with or without radiotherapy. This trial is expected to conclude in October 2018 and may help answer the question of whether it is of benefit to patients to add Zytiga (abiraterone acetate) to Taxotere (docetaxel) in metastatic disease that is still castrate-sensitive. The Phase III STAMPEDE Trial showed that adding Zytiga (abiraterone/ prednisone) to standard ADT lowered the relative risk of death by 37% and improved progression-free survival by 71%, versus ADT alone. The CHAARTED Trial looked at Taxotere (docetaxel) plus ADT or ADT alone in patients with metastatic, castrate-sensitive disease, resulting in a greater median survival in the ADT + Taxotere (docetaxel) arm (57.6 months versus 44.0 months with ADT alone).]
Learn more details about these drugs by viewing the Evidence Report from Institute for Clinical and Economic Review (ICER). ICER also held a public hearing on the topic on September 13, 2018 in Chicago.