Recent developments in advanced prostate cancer space pave way for future breakthroughs
Key takeaways:
- Combination treatment is key for patients with advanced prostate cancer.
- Researchers are analyzing genetics to figure out the role they play in treatment response.
Several practice-changing clinical trials in recent years have led to the understanding that combination treatments are most effective for patients with advanced prostate cancer.
Experts are now working to better understand the role that genetics plays in response to combination therapy.
“Over the past few years, there have been many practice-changing clinical trials that altogether clearly indicate that a combination of therapies is required for patients with advanced prostate cancer. What is now being determined is which combination therapies, in combination with testosterone suppression, should be used and how many of these treatments should be used,” Nima Sharifi, MD, scientific director of the University of Miami Miller School of Medicine’s Desai Sethi Urology Institute, said during an interview with Healio.
Role of genetics
Several ongoing international efforts are aiming to identify which patients need which treatment based on tumor biology, Sharifi told Healio.
“We have some idea of genetic changes that lead to poorer outcomes, but we don’t really know how to use that information,” he said. “What I hope will occur over the next few years is some refinement of that information so that we can use some of it to perhaps affect practice.”
In the phase 3, randomized, placebo-controlled ARCHES trial, Sharifi and colleagues sought to determine the association between the HSD3B1 genotype and outcomes among 660 men with metastatic hormone-sensitive prostate cancer assigned androgen deprivation therapy with or without enzalutamide (Xtandi; Astellas, Pfizer).
According to study results, treatment with enzalutamide led to improvements in OS, radiographic PFS and time to PSA progression compared with placebo. Of note, 31.3% of men assigned placebo crossed over to the enzalutamide regimen before disease progression.
“The key practice-changing clinical trials assessing combination treatments, such as testosterone suppression with either abiraterone [Zytiga, Janssen], enzalutamide or apalutamide [Erleada, Janssen] — or in combination with docetaxel chemotherapy — have now been done,” Sharifi said. “Now that these studies are completed, some of the investigators on these trials have collected biospecimen to analyze the genetics of disease to figure out how genetics correlate with response to particular treatments. There is a lot of work to be done to sort this all out.”
Ongoing work
Experts are now working to piece together the accumulating data on genetics in the advanced prostate cancer space.
“The ongoing work is now focused on figuring out the molecular alterations that occur that are either inherited or have come about somatically among the men enrolled and treated on these trials,” Sharifi said. “The key will be to piece together the data on genetics with the data on outcomes, and it is all very exciting.”
Researchers are focusing on the noninvasive approach to evaluating tumor genetics.
“Oftentimes, for studies that examine molecular changes or genetic changes in prostate cancer, we have to gather a sample of the tumor for localized disease, or perform biopsy for metastatic disease,” Sharifi said. “There is a lot of super exciting work that is being done specifically trying to figure out if we can, in an unbiased way, assess the genetic alterations of a tumor for someone with metastatic disease simply by using cell-free DNA. The technologic advances in that area are going to be incredibly exciting and will help advance individualized therapy for these patients.”
Other ongoing work is examining treatments in patients with metastatic castration-sensitive prostate cancer who have not been treated previously with any systemic therapies, Sharifi continued.
“Future research will include a combination of all of these advancements,” he said. “We need research to examine the technical advances in terms of detection and what the limits of detection are. We need those types of clinical trials to, at a high level, identify who benefits from what treatment and who might need other entirely different treatment. All of this is still being evaluated and we don’t yet truly know how to use that information, but with additional studies that are ongoing, I am hopeful that we will know how to use it in the very near future.”
For more information:
Nima Sharifi, MD, can be reached at nxs1664@miami.edu.
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Healio Interviews
Sharifi N, et al. J Clin Oncol. 2023;doi:10.1200/JCO.2022.40.16_suppl.5022.