Metastatic castration-resistant prostate cancer (mCRPC) is a severe and advanced stage of prostate cancer that occurs when the disease has spread beyond the prostate gland and is no longer responsive to hormonal therapy. mCRPC is incurable but treatable with a few different treatment options. Find out more about these therapies' mechanisms of action and impact on patient outcomes.
Metastatic castration-resistant prostate cancer (mCRPC) is a severe and advanced stage of prostate cancer that occurs when the disease has spread beyond the prostate gland and is no longer responsive to hormonal therapy. mCRPC is incurable but treatable, thanks to a range of effective therapies developed over the years that offer improved survival benefits and symptom control.
So with that in mind, let’s explore current and emerging therapies for mCRPC, their mechanisms of action, and their impact on patient outcomes.
Chemotherapy
Chemotherapy is a treatment that involves the use of drugs to kill cancer cells. It’s typically reserved for patients who have developed resistance to hormonal therapy.
The most commonly used chemotherapy drug for mCRPC is docetaxel, which has been shown to improve survival and quality of life in patients. But more recently, a new chemotherapy drug called cabazitaxel was approved by the FDA as a second-line treatment for mCRPC patients who have progressed on docetaxel. The drug has been shown to improve overall survival, pain control, and quality of life compared to supportive care.
Androgen Receptor-Targeted Therapy
Androgen receptor-targeted therapy is a new class of drugs that blocks the activity of the androgen receptor, which is a protein that plays a critical role in the growth and progression of prostate cancer.
Abiraterone and enzalutamide are the two most commonly used androgen receptor-targeted therapies for mCRPC. Both drugs have been shown to significantly improve survival and delay disease progression in randomized clinical trials.
Recently, a new androgen receptor-targeted therapy, apalutamide, was approved by the FDA for the treatment of non-metastatic CRPC, a condition that often progresses to mCRPC. The drug has been shown to delay the onset of metastasis and significantly improve survival compared to placebo.
Immunotherapy
Immunotherapy is a treatment approach that uses the body's natural defenses to fight cancer. In recent years, immune checkpoint inhibitors have emerged as a promising therapy for a range of cancers, including mCRPC. The drugs work by blocking certain proteins on the surface of T cells, which are a type of immune cell, that inhibit their ability to recognize and attack cancer cells.
Pembrolizumab is the first and only immune checkpoint inhibitor approved by the FDA for the treatment of mCRPC patients who have progressed on other therapies. The drug has shown significant survival benefit in a subset of patients with a high tumor mutational burden, indicating that it may be a valuable treatment option for specific patient populations.
Targeted Radionuclide Therapy
Targeted radionuclide therapy is a novel treatment approach that involves the use of radioactive isotopes to specifically target cancer cells and destroy them. In mCRPC, the most promising targeted radionuclide therapy is lutetium-177 PSMA radioligand therapy (LuPSMA). The drug targets the prostate-specific membrane antigen (PSMA), a protein that is overexpressed on the surface of prostate cancer cells.
In clinical trials, LuPSMA has shown significant efficacy in patients with advanced mCRPC, including those who have progressed on other therapies. The drug has also demonstrated excellent safety and tolerability profiles, making it a promising new treatment option for patients.
Chemotherapy, androgen receptor-targeted therapy, immunotherapy, and targeted radionuclide therapy represent some of the most promising treatment options for mCRPC patients. And as healthcare professionals, it’s essential that we stay up to date on emerging therapies and their clinical applications to provide the best possible care and outcomes for our patients.
References:
Abiraterone and increased survival in metastatic prostate cancer | Nejm. Accessed December 27, 2023. https://www.nejm.org/doi/full/10.1056/NEJMoa1014618.
Apalutamide treatment and metastasis-free survival in prostate cancer. Accessed December 27, 2023. https://www.nejm.org/doi/full/10.1056/NEJMoa1715546.
Attard G;Parker C;Eeles RA;Schröder F;Tomlins SA;Tannock I;Drake CG;de Bono JS; Prostate cancer. Lancet (London, England). Accessed December 27, 2023. https://pubmed.ncbi.nlm.nih.gov/26074382/.
Enzalutamide in metastatic prostate cancer before chemotherapy. Accessed December 27, 2023. https://www.nejm.org/doi/full/10.1056/NEJMoa1405095.
Sharma P;Retz M;Siefker-Radtke A;Baron A;Necchi A;Bedke J;Plimack ER;Vaena D;Grimm MO;Bracarda S;Arranz JÁ;Pal S;Ohyama C;Saci A;Qu X;Lambert A;Krishnan S;Azrilevich A;Galsky MD; Nivolumab in metastatic urothelial carcinoma after platinum therapy (checkmate 275): A multicentre, single-arm, phase 2 trial. The Lancet. Oncology. Accessed December 27, 2023. https://pubmed.ncbi.nlm.nih.gov/28131785/.
Sweeney CJ;Chen YH;Carducci M;Liu G;Jarrard DF;Eisenberger M;Wong YN;Hahn N;Kohli M;Cooney MM;Dreicer R;Vogelzang NJ;Picus J;Shevrin D;Hussain M;Garcia JA;DiPaola RS; Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. The New England journal of medicine. Accessed December 27, 2023. https://pubmed.ncbi.nlm.nih.gov/26244877/.
[177lu]-psma-617 radionuclide treatment in patients with metastatic ... Accessed December 27, 2023. https://www.thelancet.com/journals/lanonc/article/PIIS1470-20451830198-0/fulltext.