NEAL SHORE, MD
Atlantic Urology Clinics
Myrtle Beach, South Carolina
Shore is an internationally recognized expert and researcher with special interest in systemic therapies for patients with advanced urologic cancers affecting the prostate, kidney, and/or bladder.
Much progress has been made in the treatment of metastatic castration-resistant prostate cancer (mCRPC). As of December 2020, 9 survival-prolonging agents for mCRPC are FDA approved. However, patients with mCRPC still experience symptoms from this disease, which is not curable.
In this K-Cast video series, an expert in the management of mCRPC describes current standards in the treatment of mCRPC and provides an overview of data from the PROfound trial presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program and the European Society for Medical Oncology Virtual Congress 2020. Also discussed are genetic testing in mCRPC, the impact of coronavirus disease 2019 on patient care, the role of PARP inhibitors in patients with mCRPC, and considerations for the management of mCRPC.
This article includes highlights from 6 episodes of this K-Cast video series.
Overview of Metastatic Castration-Resistant Prostate Cancer
In terms of follow-up and evaluation of patients with mCRPC, Shore discusses any changes in symptomatology with patients and recommends imaging (conventional imaging such as CT scan and bone scan as well as next-generation imaging such as PET prostate-specific membrane antigen scan) and laboratory assessment (eg, prostate-specific antigen, complete blood count, complete metabolic profile, biomarker tests) based on patient-specific variables including disease characteristics and symptoms. When selecting among the available treatment options (including radiopharmaceuticals, taxanes, PARP inhibitors, and immunotherapy), Shore takes into account prior lines of therapy, with the goal of optimizing care and improving long-term survival.
Genetic Testing in Castration-Resistant Prostate Cancer
Genetic and molecular tests are available for patients with mCRPC. Guidelines recommend germline testing in patients with metastatic disease, and the guidelines state that somatic testing should be considered as well. Shore prefers to conduct both germline testing and somatic testing to gather as much information as possible, acknowledging that access is important and can be a limiting factor. It is important to test because the results could arguably enhance the patient-physician discussion and improve the available treatment armamentarium for patients. In May 2020, the FDA approved 2 PARP inhibitors, olaparib (Lynparza) and rucaparib (Rubraca), which clinicians can consider for patients who are navigating the mCRPC landscape.
Genetic Testing: A Conversation With Your Patient
According to Shore, it is important to be able to articulate the importance of testing—specifically genomic profiling—to patients with mCRPC. In patients with advanced disease or high-grade localized disease or in select patients with low-grade localized disease but a notable family history, Shore typically recommends somatic testing and germline testing. He initiates a conversation with patients as early as possible to allow testing of archival tissue (eg, from a biopsy or prostatectomy). Shore explains to patients that he recommends reviewing archived tissue for gene alterations and that if the patient is among the 25% affected by such alterations, treatment options are available to them.
Newly Approved Agents for Metastatic Castration-Resistant Prostate Cancer
We are currently in the era of precision therapy, notes Shore, and if a mutation in homologous recombination repair (HRR) is detected via a germline test, a somatic tissue test, or a somatic liquid test, patients with mCRPC may benefit from a PARP inhibitor. Up to 25% of patients with mCRPC have an HRR mutation and, therefore, may be candidates for a PARP inhibitor. As of December 2020, the 2 PARP inhibitors that are FDA approved for mCRPC are olaparib (Lynparza) and rucaparib (Rubraca). PARP inhibitor therapy should not obviate or negate the ability to use other approved treatments, including radiopharmaceuticals or taxane-based therapy.
A Look at the PROfound Trial
The PROfound trial (NCT02987543) evaluated olaparib, an oral PARP inhibitor dosed twice daily, in patients with mCRPC who had a qualifying HRR mutation. Enrolled patients had been heavily pretreated, all had received novel hormonal agents, and about two-thirds had received a taxane. These patients had extensive bone disease, and a high percentage also had visceral metastases. “Fortunately, what we were able to demonstrate in this study was that patients had clearly met an RPFS [radiographic progression-free survival] of a nearly 4-month benefit,” Shore says. In terms of safety and adverse events with olaparib, patients may experience myelosuppression and decreased hemoglobin and platelet counts; white blood cell counts should be monitored.
The Role of PARP Inhibitors in Prostate Cancer
PARP inhibitors have shown benefit in patients with advanced breast cancer and ovarian cancer and more recently in patients with pancreatic cancer. In the phase 3 PROfound trial, a clear survival benefit was observed with the PARP inhibitor olaparib in patients with an HRR mutation. Patients enrolled in the trial were heavily pretreated and had a heavy tumor burden. Benefits in RPFS and objective response rate were observed, predominantly driven by cohort A—patients who had mutations in BRCA2, BRCA1, or ATM. The overall safety and adverse event profiles were consistent with what has been seen with other PARP inhibitors in other tumor lines.