Personalized Treatment for Advanced Prostate Cancer: Expert Case Review

“Guiding Personalized Treatment for Advanced Prostate Cancer (Round Two)” (Andrew Armstrong) [#70] Brad Power September 27, 2023 “Many men in the community are not getting any genetic testing, especially in rural oncology or urology practices, and especially disproportionately-impacted patients such as Black men or men of lower socio-economic status.

This creates a disparity in testing but also in treatment. One message that we try to convey in discussions with patients and patient advocate societies is to ask your doctor about getting tested for both germline and tumor testing, where that can only help you.” – Andrew Armstrong “The standard of care until the last couple years has been sequential single agent therapy.

When you do that, you see very incremental improvements in survival, but it doesn't work as well as hitting the cancer hard up front with combinations when men are hormone-sensitive. In men who start their journey with metastatic hormone-sensitive prostate cancer, it's no longer standard of care to give single agent therapy such as androgen deprivation therapy (ADT) alone.

” – Andrew Armstrong “It has really radically changed in the last few years. It's no longer standard of care to offer Lupron, for example, alone, or ADT alone, but rather, treatment intensification is the standard of care for men with newly diagnosed metastatic prostate cancer.

” - Andrew Armstrong Meeting Summary Advanced prostate cancer patients want to know what their next treatment option should be if their existing treatment regimen fails. But that’s a moving target as new treatments are approved, clinical trials of new treatments start, and experience is gained in old and new treatments.

It is important to occasionally scan the range of newly approved treatments and research on treatments currently in clinical trials. For example, a number of new drug combinations and sequencing of systemic therapies in metastatic castrate-resistant prostate cancer can hit the cancer harder and earlier. Dr.

Andrew (Andy) Armstrong is uniquely qualified to talk about the latest personalized approaches to treating men with prostate cancer. (This is a follow-up to Dr. Armstrong's presentation of his research on predictive biomarkers and liquid biopsies. Please see the summary and details of meeting #64 .) Dr.

Armstrong seeks to develop and provide treatments that prolong and improve the quality of the lives of patients with aggressive prostate, kidney, bladder, and testicular cancer. His work involves the direct care of patients in the clinic and clinical research involving the development of new therapies in clinical trials.

He devotes over half of his time to understanding how prostate cancer spreads and resists therapies, as well as methods of measuring this biology in patients, which may lead to improved therapies designed to block this process.

e to understanding how prostate cancer spreads and resists therapies, as well as methods of measuring this biology in patients, which may lead to improved therapies designed to block this process. His research includes prognostic and predictive biomarkers, circulating tumor cell biology, and how cancer spreads (metastasis). He oversees multiple clinical trials of new therapies for patients ranging from new hormonal and chemotherapies to new immunotherapies, and molecularly targeted agents.

“Guiding Personalized Treatment for Advanced Prostate Cancer (Round Two)” (Andrew Armstrong) [#70] What are the trends in (prostate) cancer treatment strategies?

●Increase in treatment intensity : Treatment intensification is now standard of care for prostate cancer, involving therapy combinations of a systemic therapy, potent androgen receptor blockers, and perhaps radiating the primary site so that eventually we might be able to stop hormonal therapies.

As Bob Gatenby has shared, hitting the cancer hard and early can be more effective due to the reduced heterogeneity of your cancer population at an early stage. In addition to combinations, potent androgen receptor inhibitors are moving into earlier and earlier settings, and earlier use will have implications for subsequent therapies.

●Increase in treatment combinations: For example, combining systemic therapy and radiation can improve prostate cancer outcomes. Another example: “PARP inhibitors,” which regulate DNA repair, are being used in combination with androgen receptor inhibitors. ●Better cancer treatment outcomes for black men : Black men have better outcomes with immunotherapy and with other drugs than white men.

In a study with a double androgen receptor drug combination, black men had better outcomes with delayed progression, and better survival. The chance of making it to two years was 86% for black men and 67% for white men. ●Whole health emphasis : Men with prostate cancer are living a lot longer. Patients are enjoying remissions, but they're also suffering from the side effects of the treatments.

Lifestyle factors contribute to aggressive disease, survival, and cardiovascular risk and are reversible. There's a movement towards emphasizing the whole patient, mental health, cardiovascular health, reducing obesity, eating healthy diets, vaccinations to prevent other infectious diseases, and long term attention on bone and heart.

What are the new tests that have recently become available for prostate cancer? ●New predictive biomarkers : predictive biomarkers to guide hormonal therapy in localized prostate cancer were developed using digital pathology and artificial intelligence. ●More testing for targeted treatments : Most men in the community are not getting any testing, especially in rural and urology practices.

You should ask your doctor about getting both germline (normal tissue) and tumor testing, which can identify potential treatment options for you.

●More testing for targeted treatments : Most men in the community are not getting any testing, especially in rural and urology practices. You should ask your doctor about getting both germline (normal tissue) and tumor testing, which can identify potential treatment options for you. For example, finding a BRCA mutation through a liquid biopsy indicates likely responsiveness to PARP inhibitors.

What are the treatments that have recently become available for prostate cancer?

●New drug combinations : For example, combining androgen receptor inhibitors (like abiraterone) and PARP inhibitors (such as olaparib) for patients with metastatic castrate- resistant prostate cancer, especially for patients with a BRCA mutation, can block DNA repair and kill the cancer cells with overwhelming DNA mutations.

“Guiding Personalized Treatment for Advanced Prostate Cancer (Round Two)” (Andrew Armstrong) [#70] have faulty DNA repair, which can be encouraged by inhibiting the androgen receptor and the PARP enzyme. What are the treatments that are in the research phase for prostate cancer?

●Immunotherapy and other treatment combinations : Therapies leveraging the immune system have demonstrated huge successes in non-small cell lung, small cell lung, kidney, and bladder cancers.

Researchers are trying to find similar results from combining immunotherapies with other treatment options in other cancers and developing ways to draw T-cells into tumors to overcome cancer recognition by the immune system.

●New treatments for neuroendocrine cancer : Neuroendocrine prostate cancer, a rare and aggressive form of prostate cancer, needs more research and advocacy to improve treatment options. Research on immunotherapy and platinum-based chemotherapy for neuroendocrine prostate cancer is showing mixed results.

Researchers are targeting neuroendocrine prostate cancer with unique cell surface receptors (like bombesin). It's the first time it's ever been done.

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You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Guiding Personalized Treatment for Advanced Prostate Cancer (Round Two)” (Andrew Armstrong) [#70] Meeting Notes KEYWORDS patients, parp inhibitor, study, prostate cancer, combinations, therapy, ar, cancer, survival, inhibitors, men, metastatic, mutations, trial, years, questions, metastases, delay, african ancestry, progression SPEAKERS Andy Armstrong (87%), Brad Power (9%), Allen Morris (2%), John Sandiford (1%), David Plunkett (<1%). OUTLINE 1.Prostate cancer re

combinations, therapy, ar, cancer, survival, inhibitors, men, metastatic, mutations, trial, years, questions, metastases, delay, african ancestry, progression SPEAKERS Andy Armstrong (87%), Brad Power (9%), Allen Morris (2%), John Sandiford (1%), David Plunkett (<1%). OUTLINE 1.Prostate cancer research and treatment. (0:03) 2.Prostate cancer treatment advancements and clinical trials. (1:12) 3.

Prostate cancer treatment strategies and survivorship. (7:08) 4.Prostate cancer therapies and DNA repair. (11:58) 5.PARP inhibitors for prostate cancer treatment. (17:17) 6.Prostate cancer treatment options and research. (22:41) 7.Prostate cancer therapies and clinical trials. (26:58) 8.Prostate cancer treatment strategies and nomograms. (33:27) 9.Developing prostate cancer survival models.

(38:52) 10.Prostate cancer treatment options and darolutamide efficacy. (43:57) 11.Personalized cancer treatment strategies. (48:28) SUMMARY ●Prostate cancer research and treatment. 0:03 ○Andy Armstrong shares more research and ideas on prostate cancer in a follow- up session. ●Prostate cancer treatment advancements and clinical trials.

1:12 ○Andy Armstrong discusses prostate cancer research at Duke University, highlighting the use of potent AR inhibitors and multidisciplinary care for advanced disease. ○Armstrong presents findings on disparities in black men with aggressive prostate cancer, including unique outcomes from trials at Duke.

○Andy Armstrong discusses the latest advancements in prostate cancer treatment, including new combination therapies and the importance of early detection. ○He highlights the need for improved screening and early detection programs in emerging economies to reduce the prevalence of metastatic disease. ●Prostate cancer treatment strategies and survivorship.

“Guiding Personalized Treatment for Advanced Prostate Cancer (Round Two)” (Andrew Armstrong) [#70] ○Treatment intensification is now standard of care for prostate cancer, often involving potent AR blockers or triple therapy. ○Dr. Armstrong highlights the need for combined systemic therapy and radiation to improve prostate cancer outcomes. ●Prostate cancer therapies and DNA repair.

11:58 ○Andy Armstrong highlights the limited survival improvement of FDA-approved life-prolonging therapies for prostate cancer, with an average of 4-5 months of extra life. ○He advocates for comprehensive germline and tumor testing to identify potential treatment options for patients, including PARP inhibitors and liquid biopsy.

○He explains how combining AR and PARP inhibitors can lead to cancer cell death by overwhelming DNA repair errors. ●PARP inhibitors for prostate cancer treatment. 17:17 ○Andy Armstrong discusses a global study on metastatic castrate resistant prostate cancer patients, with a focus on the impact of PARP inhibitors on overall survival.