Rashid K. Sayyid, MD, MSc

Rashid K. Sayyid, MD, MSc, discusses the role of combination therapy in metastatic castrate-resistant prostate cancer.

The Role of Combination Therapy in mCRPC

This is a synopsis of an Educated Patient Sound Bites series featuring Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute; Rashid K. Sayyid, MD, MSc, of the University of Toronto; and Reginald Tucker-Seeley, MA, ScM, ScD, of ZERO Prostate Cancer.

Dr Rashid K. Sayyid discusses PARP inhibitors like olaparib and rucaparib in combination with other therapies. For example, enzalutamide-olaparib was approved based on TRITON3 for certain mutations, while olaparib-abiraterone was approved first-line for 

-mutated cancer per PROPEL. He explains PARP inhibitors may radiosensitize, improving radium Ra 223 dichloride efficacy.

The ongoing COMRADE phase 1/2 trial established olaparib-radium dosing in phase 1 and showed 6-month 57% radiographic progression-free survival and 56% 1-year overall survival. Phase 2 is now examining olaparib-radium efficacy for radiographic progression-free survival with 213 patients. Upcoming results over next few years.

In summary, Dr. Sayyid overviews emerging prostate cancer approaches, including PARP inhibitor combinations with antiandrogens like enzalutamide or abiraterone for certain mutations, as well as combinations with radium Ra 223 dichloride now under phase 2 investigation.

*Video synopsis is AI-generated and reviewed by CURE editorial staff.

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Rashid K. Sayyid, MD, MSc, gives a brief overview of treatment options for nonmetastatic castrate-resistant prostate cancer.

Treatment Options for Nonmetastatic CRPC

Dr Rashid K. Sayyid defines nmCRPC [non-metastatic castration-resistant prostate cancer] as evidence of castration resistance without metastases on CT or bone scan. He notes recent progress in nmCRPC treatment, with FDA approval of second-generation antiandrogens apalutamide, enzalutamide, and darolutamide along with continued androgen deprivation therapy (ADT). Approvals were based on the phase 3 ARAMIS, PROSPER, and SPARTAN trials respectively.

The ARAMIS trial randomized patients with nmCRPC with rapidly rising prostate-specific antigen (PSA) to darolutamide or placebo plus ADT. Metastasis-free survival increased from 18 to 40 months with darolutamide, reducing death risk by 31%. Similarly, the PROSPER trial using enzalutamide improved metastasis-free and overall survival by 11 months. Finally, the SPARTAN trial with apalutamide extended metastasis-free survival by 2 years and overall survival over 1 year.

In summary, Dr Rashid K. Sayyid reviews recent progress in treating non-metastatic castrate-resistant prostate cancer with second-generation antiandrogens apalutamide, enzalutamide, and darolutamide. The phase 3 ARAMIS, PROSPER, and SPARTAN trials supported FDA approval.

Expert perspectives on the treatment approach for patients with metastatic castrate-resistant prostate cancer.

Treatment Approach for Patients With Metastatic CRPC

Dr Rashid K. Sayyid overviews radium Ra 223 dichloride, approved in 2013 for bone metastases based on the ALSYMPCA trial showing improved survival by 3 months. The ongoing REASSURE observational study recently showed 16-month median overall survival, 35% rate of adverse events, and reduced pain scores.

Dr Sayyid then covers Lutetium Lu 177-PSMA-617, approved for prostate-specific membrane antigen (PSMA) positive mCRPC after chemotherapy and antiandrogens. The VISION and TheraP trials support Lu 177-PSMA-617 efficacy. Ongoing trials like SPLASH may soon move it earlier in treatment lines.

PARP inhibitors like olaparib, rucaparib, and talazoparib are also discussed. The PROfound trial showed olaparib improves survival by 3.5 months for 

–mutated mCRPC after antiandrogens, supporting 2020 approval. Similarly, the TRITON2 trial supported rucaparib third-line approval after chemotherapy and antiandrogens improved imaging-based progression-free survival.

In summary, Dr Rashid K. Sayyid overviews promising first/second-line castration-resistant prostate cancer treatments like radium Ra 223 dichloride, Lutetium Lu 177-PSMA-617 for PSMA positive disease, and PARP inhibitors olaparib and rucaparib.

An expert on prostate cancer gives a brief overview of castrate-resistant prostate cancer.

Overview of Castrate-Resistant Prostate Cancer (CRPC)

Dr Rashid K. Sayyid defines castrate-resistant prostate cancer as cancer cells continuing to grow despite testosterone suppression below castration levels. He states cells can become resistant to hormone therapy over time.

Castrate resistance is defined as prostate-specific antigen (PSA) increasing 25% over several weeks to an absolute value above 2 ng/mL, along with testosterone levels not being fully suppressed. Dr Sayyid notes castrate-resistant prostate cancer comprises both non-metastatic and metastatic disease, with distinction based on CT and bone scan versus PET imaging.

In summary, Dr Rashid K. Sayyid covers the definition of castrate-resistant prostate cancer, how it develops resistance to hormone therapy, diagnostic criteria involving rising PSA with testosterone not fully suppressed, and how it is categorized into non-metastatic and metastatic disease based on CT, bone scan and PET imaging findings.

Rashid K. Sayyid, MD, MSc

The Role of Combination Therapy in mCRPC

Treatment Options for Nonmetastatic CRPC

Treatment Approach for Patients With Metastatic CRPC

Overview of Castrate-Resistant Prostate Cancer (CRPC)

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