Despite the potential for clinical benefit, triplet therapies have added complexities, monitoring needs, toxicities, and costs associated with additional pharmacologic therapy.
Triplet drug therapies have become the standard of care for many types of cancer over the past several years, explained Brian Fitzgerald, PharmD, BCOP, during his presentation at the HOPA Annual Conference 2023. In 2022, authors of the PEACE-1 (NCT01957436) and ARASENS (NCT02799602) trials advocated for the use of triplet therapy in patients with metastatic castration-sensitive prostate cancer. However, Fitzgerald noted that despite the potential for clinical benefit, triplet therapies have added complexities, monitoring needs, toxicities, and costs associated with additional pharmacologic therapy.
“Triplet therapy has really moved the needle for a lot of cancer types in their treatments, [such as for] lung cancer, colon cancer, and myeloma,” Fitzgerald said. “But prostate cancer hadn't really had its moment with triplet therapy—but now we do.”
Prostate cancer is the most common malignancy in US males, according to Fitzgerald. In 2022, there were approximately 268,490 new cases, and approximately 34,500 deaths. Further, the 5-year survival rate for prostate cancer as a whole is pretty favorable, with 97% of patients alive at 5 years and 32.3% metastatic.
“We have to take into consideration that that's driven mainly by the high proportion of localized disease that we see in patients who will receive definitive and curative therapies,” Fitzgerald said. “I would be remiss if I didn't mention one of the biggest risk factors in developing prostate cancer, which is race. Patients of African ancestry are at a higher risk of developing prostate cancer. Not only that, but they're at a higher risk of developing more advanced types of prostate cancer, being diagnosed with prostate cancer at a younger age, and more than twice as likely to die from prostate cancer as other races.”
These data are important to keep in mind when developing prostate cancer trials, according to Fitzgerald. Patients with higher risk of prostate cancer, such as those with African ancestry, should be included in clinical trials, because they're going to be the ones gaining the most benefiting from advancements in treatment.
“So 2 terms that you may know about or may hear with prostate cancer is the concept of castration-sensitive disease and castration-resistant disease,” Fitzgerald said. “So patients in [the castration-sensitive disease] setting are sensitive to castration levels of testosterone. So in advanced prostate cancer treatment, our mainstay of treatment is going to be hormonal deprivation and, because testosterone and androgens are the primary growth pathway for prostate cancer cells, our mainstay of treatment for this population is going to be depriving those prostate cancer cells of testosterone and estrogens.”
Following the PEACE-1 and ARASENS trials, the 2 triplet therapy regimens recommended for metastatic castration-sensitive prostate cancer are androgen deprivation therapy (ADT) plus docetaxel (Docefrez; Sun Pharmaceutical Industries) plus abiraterone (Zytiga; Centocor Ortho Biotech) or ADT plus docetaxel plus darolutamide (Nubeqa; Bayer).
“[In the NCCN guidelines for metastatic castration sensitive patients,] it's not explicitly said that [there’s a] high versus low volume split,” Fitzgerald said. “But if you look at the footnote in the NCCN guidelines itself, with the triplet therapy regimen, it does have language there that says that the panel encourages the use of triplet therapy for patients who have that high volume of disease. So that would be one way to tease out the decision-making process with these conditions.”
Although the results of the PEACE-1 and ARASENS trials support the use of triplet therapy in this patient population, disease volume remains important to consider.
“Something else to think about with triplet therapy are not only the survival benefit we see with adding all these agents upfront, but also taking into account the different toxicities, the costs, complexities, and challenges in monitoring that have to be done,” Fitzgerald said. “Pharmacists are really kind of at the forefront keeping these things in mind when we're starting patients on all these different medications, activity monitoring, doing follow up assessment calls, helping with co-pay assistance, and all these different processes.”
Fitzgerald B. Three’s a Crowd: Triplet Therapy for Metastatic Prostate Cancer. Presented at HOPA Annual Conference 2023 in Phoenix, AZ; March 31, 2023.