Leonard G. Gomella, MD, Tanya Dorff, MD, Scott Eggener, MD, and Jorge Garcia, MD, all reflect on prostate cancer treatment in 2019.
"The development of all the new targeted therapies based on genetics for advanced prostate cancer is going to be the next big breakthrough. Understanding the genetics involved and the development of precision medicine are all wrapped up together.
The therapies are not out yet, but they should be available either late this year or early next. The drugs are called PARP inhibitors and are in late-stage studies. They’ll be the first drugs for prostate cancer that are specifically targeted to common inherited genetic abnormalities.
These drugs are known to have activity in breast and ovarian cancer, which we’ve discovered share common genetic alterations with prostate cancer. These drugs will be used to treat prostate cancer patients who have specific mutated genes in the DNA repair pathways.
Our cancer center has been involved with one of the PARP inhibitor studies. This class of drug is at the FDA being evaluated, and several agents are being fast tracked.
It’s going to be great because it gives patients who have advanced prostate cancer a whole new approach to treatment that we’ve never had before. These drugs represent the first truly precision treatment for advanced prostate cancer.”
Leonard G. Gomella, MD
Thomas Jefferson University, Philadelphia
Next: "Probably the most important advance comes from the PROfound trial just reported at the European Society for Medical Oncology annual meeting"
"Probably the most important advance comes from the PROfound trial just reported at the European Society for Medical Oncology annual meeting in Barcelona. It’s the first randomized, head-to-head trial comparing olaparib [Lynparza], a PARP inhibitor, to more standard drugs, abiraterone [ZYTIGA] and enzalutamide [XTANDI] in men already treated with one of these agents. We’ve had hints it might be effective, but that olaparib is more effective than sequential use of abiraterone/enzalutamide is groundbreaking.
Previously, we’ve only seen phase II data. With the phase III data, I anticipate FDA will approve olaparib for men with metastatic, castration-resistant prostate cancer with specific DNA mutations (BRCA and others used to select men for trial enrollment). So we’ll have a new treatment not available before.
Not everyone will benefit, but this highlights the importance of DNA sequencing in all metastatic prostate cancer patients, because men with certain mutations now have an extra line of therapy to increase their survival.
The study showed the median time for cancer to progress was 7.39 months with olaparib, versus 3.55 months with standard treatments, significantly improving the time cancer was under control. Survival was prolonged as well. It was 18½ months versus 15 months.
The next generation of PARP inhibitors is being tested already but they won’t be compared against olaparib, so we won’t know immediately whether they are better. It’s hoped some may be even more effective.”
Tanya Dorff, MD
City of Hope Comprehensive Cancer Center, Duarte, CA
Next:"A recent study in JAMA suggests men with African ancestry do not appear to have worse outcomes with prostate cancer surveillance or treatment than other men"
"There are recent notable advances for metastatic prostate cancer treatment, but there are also advances in non-metastatic prostate cancer care.
We’ve always been taught black men have a higher likelihood of being diagnosed with, and dying of, prostate cancer and consequently, we need to be more aggressive in screening and treatment, with reservations about active surveillance. However, a recent study in JAMA suggests men with African ancestry do not appear to have worse outcomes with prostate cancer surveillance or treatment than other men.
In a well-done observational study of approximately 300,000 men, once they factored in socioeconomic status, access to care, and standardized treatment, long-term cancer-related outcomes were similar based on race.”
For those of us who care for a significant number of men of African ancestry, it suggests we don’t need to be more concerned about an aggressive natural history of the cancer based on race. Many urologists are reluctant to offer active surveillance to black men based on previous concerns the disease could be more aggressive and surveillance might not be effective. But if a man has low-risk prostate cancer, active surveillance should be strongly considered, and race alone shouldn’t impact that decision.
Similarly, for men of African ancestry who do require treatment, it suggests you don’t necessarily need an escalation of treatment or combination of therapies.”
Scott Eggener, MD
University of Chicago Medicine, Chicago
Next: "If I were to take my pick, it’s the European PROfound phase III study of olaparib, a PARP inhibitor, compared to enzalutamide."
"If I were to take my pick, it’s the European PROfound phase III study of olaparib, a PARP inhibitor, compared to enzalutamide.
This is the first positive biomarker-selected, phase III trial assessing the efficacy of a therapeutic agent driven by the molecular phenotype of patients with metastatic, castration-resistant prostate cancer. That’s huge.
Obviously, this study highlights the importance of genomics in men with prostate cancer, and as a potential therapeutic target for the FDA to approve, it changes the landscape for patient management.
Olaparib is already approved in the United States for women with ovarian cancer who harbor a BRCA mutation. That’s one way our guidelines for prostate cancer patients are changing. Now, we’re testing the vast majority of men with either high-risk or advanced prostate cancer, because we recognize that up to 10% of men may have DNA-repair deficiencies, specifically BRCA mutations, from birth.
We did not participate in this trial, but we have clinical experience using this type of agent for the patient population in question, in what you would call off-label use. The data is striking for patients with that sort of DNA deficiency.”
Jorge Garcia, MD
Cleveland Clinic, Cleveland
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