mCRPC – PROVENGE (sipuleucel-T)

What is mCRPC?

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced stage of prostate cancer that has spread to different parts of the body. At this stage, it doesn’t respond to the usual hormonal therapy called androgen deprivation therapy (ADT). Even with low testosterone levels achieved through surgical or medical castration, mCRPC continues to grow and spread. As the disease progresses, it presents new treatment options that require careful consideration.

Risk Factors and Causes

Several risk factors contribute to the development of mCRPC. These may include age, family history of prostate cancer, select genetic mutations, and exposure to certain environmental factors. While the exact causes of mCRPC are still being studied, more research is needed to fully understand its origins.

Progression of Prostate Cancer to mCRPC

Role of Androgens and Androgen Receptors

Androgens, such as testosterone, play a crucial role in the growth and function of the prostate gland. Androgens also play a role in the growth and survival of prostate cancer cells by interacting with androgen receptors present on the cells. When the prostate cancer cells are still sensitive to androgens, prostate cancer treatment (eg, hormone therapy) aims to either suppress androgen production or block androgens from acting on the receptors to impede the growth of prostate cancer cells. However, as time goes by, certain cancer cells can acquire resistance to this therapy, allowing the cancer to progress.

This progression can take different paths. In some cases, the cancer cells may develop the ability to grow and metastasize, spreading to other parts of the body. This is when it becomes metastatic prostate cancer. On the other hand, the cancer cells can also become resistant to the hormonal therapy, known as castration resistance. This means that despite low levels of androgens achieved through surgical or medical castration, the cancer cells continue to thrive and proliferate.

It’s important to note that not all prostate cancer cases progress to mCRPC or develop metastases. Each patient’s journey is unique, and their response to treatment can vary. However, in cases where the cancer becomes resistant to hormonal therapy and starts to metastasize, the condition is referred to as mCRPC. This indicates alternative treatment approaches are needed to effectively target castration resistant or metastatic disease.

Mechanisms of Resistance to Androgen Deprivation Therapy (ADT)

Resistance to ADT (also known as hormone therapy) can occur through various mechanisms. These include alterations in androgen receptor signaling pathways, mutations in the androgen receptor gene, increased androgen receptor expression, or activation of alternative signaling pathways that bypass the need for androgens. These changes allow cancer cells to survive and grow despite low levels of androgens.

Emergence of Castration-Resistant Prostate Cancer Cells

In mCRPC, prostate cancer cells become resistant to hormone therapy and become aggressive, that is they gain the ability to multiply and spread even when androgens are present. This aggressive behavior is often because genetic and epigenetic factors allow the cells to adapt to new treatment challenges.

Clinical Features of mCRPC

Biomarkers and advanced imaging techniques play a crucial role in the diagnosis, monitoring, and management of mCRPC. These tools help to identify specific genetic alterations, detect the spread of cancer to other sites, and assess treatment response. Biomarker tests, such as prostate-specific antigen (PSA) levels, and imaging modalities like bone scans and positron emission tomography (PET) scans, aid in the evaluation of disease progression and guide treatment decisions.

mCRPC can present with various clinical manifestations, which may include bone pain, fractures, urinary symptoms, fatigue, weight loss, and anemia. These symptoms may vary depending on the extent and location of metastases.

Complications of mCRPC may include bone metastases, spinal cord compression, urinary obstruction, and the development of secondary cancers. Managing these complications is an important aspect of comprehensive mCRPC care.

mCRPC Treatment Options

Several treatment options are available for mCRPC, and the choice of treatment depends on individual patient characteristics, disease stage, and previous therapies.

Androgen Receptor Signaling Inhibitors

Targeted therapies that work by blocking the androgen receptor or inhibiting androgen production. These medications help to suppress the growth and spread of cancer cells and can provide clinical benefits for patients with mCRPC. These are different from the hormonal therapy that you may continue to receive as determined by your physician.

Immunotherapy

A type of cancer treatment that helps your immune system fight cancer. There are several different types of immunotherapy (for example, cellular therapies, CAR-T therapies, and checkpoint inhibitors) and each work differently. Certain immunotherapeutic agents, like PROVENGE, aim to boost the body’s immune system to recognize and destroy cancer cells; showing promising results in the treatment of mCRPC.

Targeted Therapies

Therapies that specifically target molecules or pathways involved in cancer growth and survival. These therapies may be used to inhibit specific genetic alterations or signaling pathways that are driving the progression of mCRPC.

Chemotherapy

The use of drugs that kill or inhibit the growth of cancer cells. Chemotherapy may be administered in combination with other therapies or as a standalone treatment, depending on the individual patient’s circumstances.

mCRPC represents an advanced stage of prostate cancer that poses unique challenges in treatment. Understanding its progression, clinical features, and available treatment options is crucial for healthcare professionals and patients in making informed decisions about managing this complex disease. By leveraging therapies and personalized treatment approaches, there is hope for improved outcomes and enhanced quality of life for individuals living with mCRPC.

References

1 PROVENGE [prescribing information]. Seal Beach, CA: Dendreon Pharmaceuticals LLC; 2017.

2 Madan RA, Gulley JL, Fojo T, Dahut WL. Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression. Oncologist. 2010;15(9):969-975. doi:10.1634/theoncologist.2010-0129

3 Higano CS, Armstrong AJ, Sartor AO, et al. Real-World Outcomes of Sipuleucel-T Treatment in PROCEED, a Prospective Registry of Men With Metastatic Castration-Resistant Prostate Cancer. Cancer. 2019 Dec 1;125(23): 4172-4180. doi: 10.1002/cncr.32445. Epub 2019 Sep 4.

4 Smith MR, Saad F, Chowdhury S, et al; SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378(15):1408-1418. doi:10.1056/NEJMoa1715546

INDICATION

PROVENGE^® (sipuleucel-T) is a prescription medicine used to treat certain men with advanced prostate cancer. PROVENGE is an established cellular immunotherapy and is customized to each individual by using his own immune cells.

IMPORTANT SAFETY INFORMATION

Before receiving PROVENGE^®, tell your doctor about any medical conditions, including heart or lung problems, or if you have had a stroke.

Tell your doctor about any medicines you take, including prescription and nonprescription drugs, vitamins, or dietary supplements.

The most common side effects of PROVENGE include chills, fatigue, fever, back pain, nausea, joint ache, and headache. These are not all the possible side effects of PROVENGE treatment.

PROVENGE is made from your own immune cells, which are collected during a process called leukapheresis. The cells are processed, returned, and then infused back into the patient through an IV (intravenous) infusion about 3 days later. This process is completed in 3 cycles, about 2 weeks apart. Each infusion takes approximately 1 hour and requires 30 minutes of post-infusion monitoring.

PROVENGE infusion can cause serious reactions. Tell your doctor right away if you:

Have signs of a heart attack or lung problems, such as trouble breathing, chest pains, racing or irregular heartbeats, high or low blood pressure, dizziness, fainting, nausea, or vomiting
Have signs of a stroke, such as numbness or weakness on one side of the body, decreased vision in one eye, or difficulty speaking
Develop symptoms of thrombosis which may include: pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, shortness of breath, chest pain that worsens or deep breathing
Have signs of infection such as a fever over 100°F, redness or pain at the infusion or collection sites

Tell your doctor about any side effect(s) that concerns you or does not go away. For more information, talk with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Full Prescribing Information.

To report an adverse event, please email our Pharmacovigilance department at drugsafety@dendreon.com, or fax adverse event details to 833-464-0123. Please provide details pertaining to the adverse event and provide contact information so that our Pharmacovigilance team may contact you with any questions.

To report a product complaint, email our Quality department at CQAcomplaints@dendreon.com. Please provide details pertaining to the quality issue and provide contact information so that our Quality team may contact you with any questions.

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