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Breakthroughs in Prostate Cancer: Latest Studies on Enzalutamide, PARPi, and Immunotherapy

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Last Updated on December 23, 2023 by Max

Introduction

Welcome to our new section, “Latest Research and Developments,” a regular feature on our blog dedicated to the most recent and impactful scientific advancements in the world of men’s health. This section will serve as a dynamic resource, bringing you comprehensive reviews of crucial scientific articles and clinical trials focused on prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis, and overall wellness in men’s health. We aim to keep you informed about the latest breakthroughs, offering insights into emerging treatments, innovative therapies, and key developments in medical research.

In today’s post, we delve into some of the latest studies in prostate cancer treatment. We explore the efficacy and safety of enzalutamide in various forms, including in combination with androgen deprivation therapy and as a standalone option. We also examine the promising role of Poly-ADP ribose polymerase inhibitors (PARPi) in treating metastatic castrate-resistant prostate cancer and the potential of new immunotherapies in tackling high-risk prostate cancers. Additionally, we discuss advancements in hormone therapy for advanced metastatic prostate cancer, highlighting the benefits of new drug combinations.

Join us on this journey through the forefront of men’s health research, where each post promises to bring clarity and understanding to the complex world of medical advancements

Review 1: New Treatment Options for Aggressive Prostate Cancer

A short video version of the study you can watch here.

Published on: October 18, 2023

Overview: mCRPC, or metastatic castrate-resistant prostate cancer, occurs when initial hormonal therapies, typically used as the primary treatment for metastatic prostate cancer, cease to be effective. These initial drugs work by reducing the body’s production of testosterone, a hormone that accelerates the growth of prostate cancer. Once these therapies lose their effectiveness, physicians transition to a different category of medications known as anti-androgens. These drugs continue to suppress testosterone by obstructing its receptor in the cells. Enzalutamide is one such anti-androgen drug used in this later stage of treatment. In an impactful Phase III clinical trial involving 1,068 patients, researchers at Cedars-Sinai Cancer have introduced two novel treatments for men with high-risk, biochemically recurrent prostate cancer. The study focuses on the efficacy and safety of enzalutamide, both in combination with and as an alternative to androgen-deprivation therapy (ADT), compared with ADT alone.

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Treatments and Trial

  • Enzalutamide Plus ADT: Patients in this group received 160 mg of enzalutamide daily combined with leuprolide, a medication administered every 12 weeks.
  • Enzalutamide Monotherapy: This group received only enzalutamide, relying on its ability to block testosterone’s effects without reducing blood testosterone levels.
  • Control Group: The control group received the current standard of care, ADT alone (leuprolide).

Results and Effectiveness

  • At 5 years, metastasis-free survival was 87.3% in the enzalutamide plus ADT group, compared to 71.4% in the ADT-alone group.
  • Enzalutamide monotherapy showed a metastasis-free survival rate of 80.0%.
  • Enzalutamide plus ADT reduced the risk of metastasis or death by 57.6%, and enzalutamide alone by 36.9%, both significant improvements over ADT alone.
  • The safety profile of enzalutamide was consistent with previous studies, with no apparent detrimental effect on quality of life.

Key Findings: The trial demonstrated a substantial reduction in the risk of disease progression or death when enzalutamide was used either in combination with ADT or as a monotherapy. Both treatment approaches significantly delayed the need for new antineoplastic therapy and the time to PSA progression. No substantial differences in quality-of-life measures were observed between the treatment groups and the control group. The study highlights enzalutamide’s potential as an effective treatment for high-risk biochemical recurrence in prostate cancer, with a safety profile that does not compromise patients’ quality of life.

Implications for Prostate Health: This study is a significant stride forward in the treatment of aggressive prostate cancer, particularly in cases of biochemical recurrence. These results present new therapeutic options that could enhance patients’ quality of life while effectively managing the disease.

Enzalutamide, known by the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) specifically used to treat prostate cancer. It works by blocking the effects of androgens (like testosterone) by directly inhibiting the androgen receptor, thereby reducing the stimulation of cancer cells. Approved for the treatment of metastatic castration-resistant prostate cancer, it has also shown efficacy in trials for non-metastatic and metastatic hormone-sensitive prostate cancer.

Leuprolide, also known by the brand name Lupron, is a type of hormone therapy used in the treatment of prostate cancer. It belongs to a class of drugs known as gonadotropin-releasing hormone (GnRH) agonists. Leuprolide reduces the production of testosterone in men, which helps slow the growth of testosterone-dependent cancer cells. Commonly used in androgen deprivation therapy (ADT), it’s effective in reducing the growth-stimulating effects of testosterone on prostate cancer cells.

In the study, Enzalutamide was tested both in combination with Leuprolide and as a standalone treatment. The combination aimed to block the effects of any remaining testosterone after ADT (Leuprolide) and directly inhibit the androgen receptor (Enzalutamide). On the other hand, Enzalutamide monotherapy tested the efficacy of blocking androgen receptors without reducing testosterone levels.

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Conclusion: The trial’s findings underscore the potential of enzalutamide, either in combination with ADT or as a standalone treatment, to improve outcomes for patients with high-risk biochemical recurrence of prostate cancer. These results are promising for the future of prostate cancer treatment, offering new hope and options for patients and healthcare providers.

Review 2: PARP Inhibitors in Metastatic Prostate Cancer

Published on: Apr 24, 2023 

Overview: Recent studies have highlighted the effectiveness of Poly-ADP ribose polymerase inhibitors (PARPi) in treating prostate cancer. These inhibitors work by inducing synthetic lethality in cells with deficiencies in homologous recombination repair (HRR), particularly beneficial in men with metastatic castrate-resistant prostate cancer (mCRPC) and select HRR pathway alterations. The FDA-approved PARPi for mCRPC includes olaparib and rucaparib, showing improvements in tumor response, progression-free, and overall survival.

Key Studies

  • TOPARP-A Trial (Olaparib): This Phase II trial focused on patients with mCRPC, where olaparib induced a response rate of 33%, with a median duration of response of 40 weeks.
  • PROfound Study: A Phase III trial that showed significant increases in radiographic progression-free survival (rPFS) in the olaparib arm compared to the control. Median overall survival in cohort A was 19.1 months for olaparib, a notable improvement.
  • TRITON2 Study (Rucaparib): This study led to accelerated FDA approval of rucaparib for patients with mCRPC and BRCA1/2 alteration, demonstrating prolonged rPFS compared to controls.

Implications: PARPi therapy has emerged as a vital treatment for a subset of patients with mCRPC, offering new hope and improved outcomes.

Review 3: Immunotherapy for High-Risk Prostate Cancers

Published on: 03 April 2023 

Overview: A Phase II study led by Johns Hopkins Kimmel Cancer Center has shown that a new drug, enoblituzumab, is safe and potentially effective in men with aggressive prostate cancer. This monoclonal antibody targets the protein B7-H3, overexpressed in prostate cancer cells.

Study Details: 32 men with high-risk or very high-risk prostate cancers received six weekly infusions of enoblituzumab before surgery. 66% had an undetectable PSA level 12 months following surgery, indicating no residual disease. Enoblituzumab was well-tolerated, with mild side effects like fatigue and flu-like symptoms. If confirmed in larger studies, enoblituzumab could become a pivotal antibody-based immunotherapy against prostate cancer, offering a new pathway for treatment.

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Review 4: Hormone Therapy for Advanced Metastatic Prostate Cancer

Published on: June 20, 2023

Overview: The FDA has approved a combination of enzalutamide (Xtandi) with talazoparib (Talzenna) as an initial treatment for some people with metastatic castration-resistant prostate cancer, which has spread and no longer responds to standard hormone-blocking treatments.

Clinical Trial Findings: Patients treated with the combination lived longer without their cancer worsening than those treated with enzalutamide alone. About 50% of patients with specific gene alterations were alive without cancer progression nearly 3 years after starting treatment. Patients receiving the combination reported better quality of life compared to those on enzalutamide alone. The combination therapy showed more severe side effects than standard treatment, including anemia and fatigue. This combination represents a significant advancement in treating metastatic castration-resistant prostate cancer, particularly for patients with specific genetic alterations.

Don’t keep your thoughts to yourself—join the conversation! Share your experiences, questions, and insights in the comments below. Together, we can make a difference in the lives of those affected by prostate issues. Let’s empower each other and create a supportive community! Comment now!


References for the Study Reviews

  • Freedland, S. J., de Almeida Luz, M., De Giorgi, U., Gleave, M., Gotto, G. T., Pieczonka, C. M., Haas, G. P., Kim, C.-S., Ramirez-Backhaus, M., Rannikko, A., Tarazi, J., Sridharan, S., et al. (2023). Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. New England Journal of Medicine. DOI: 10.1056/NEJMoa2303974.
  • Taylor AK, Kosoff D, Emamekhoo H, Lang JM, Kyriakopoulos CE. PARP inhibitors in metastatic prostate cancer. Front Oncol. 2023 Apr 24;13:1159557. doi: 10.3389/fonc.2023.1159557. PMID: 37168382; PMCID: PMC10165068.
  • Shenderov, E., De Marzo, A.M., Lotan, T.L. et al. Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial. Nat Med 29, 888–897 (2023). https://doi.org/10.1038/s41591-023-02284-w.
  • FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. 

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