Dr Sharma on Questions Regarding the Optimal Use of Triplet Therapies in HSPC

Janaki Neela Sharma, MD, assistant professor, genitourinary oncology, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses data on the use of triplet therapies in patients with hormone-sensitive prostate cancer (HSPC), highlighting unanswered questions regarding triplet vs doublet treatment options for patients whose disease is not considered high risk.

The phase 3 PEACE-1 (NCT01957436) and ARASENS (NCT02799602) trials demonstrated the survival benefit associated with adding an androgen receptor pathway inhibitor (ARPI) to standard-of-care (SOC) therapy vs SOC alone for patients with prostate cancer, Sharma says. PEACE-1 evaluated treatment with SOC (n = 296; defined as androgen deprivation therapy [ADT] alone or in combination with docetaxel) vs SOC plus radiotherapy (n = 291) vs SOC plus abiraterone acetate (Zytiga; n = 292) vs SOC plus radiotherapy and abiraterone (n = 291) in patients with metastatic castration-resistant prostate cancer.

In the overall population, at a median follow-up of 3.5 years (IQR, 2.8-4.6), the median radiographic progression-free survival was longer among patients who received abiraterone (n = 583) than those who did not receive abiraterone (n = 589; HR, 0.54; 99.9% CI, 0.41-0.71; P < .0001). At a median follow-up of 4.4 years (IQR, 3.5-5.4), the median overall survival (OS) was longer among patients treated with abiraterone vs those not treated with abiraterone (HR, 0.75; 95.1% CI, 0.59-0.95; P < .017).

The ARASENS trial randomly assigned patients with metastatic HSPC to receive either darolutamide (Nubeqa; n = 651) or placebo (n = 655), both in combination with docetaxel and ADT. The addition of darolutamide to docetaxel and ADT reduced the risk of death by 32.5% vs placebo (HR, 0.68; 95% CI, 0.57-0.80; P < .001). The 4-year OS rates in the darolutamide and placebo arms were 62.7% (95% CI, 58.7%-66.7%) and 50.4% (95% CI, 46.3%-54.6%), respectively.

Although both PEACE-1 and ARASENS met their primary end points, these trials were not designed to determine whether docetaxel plus an ARPI is superior to an ARPI alone in patients with HSPC, Sharma explains. Therefore, the optimal treatment for patients with HSPC who do not have high-risk disease remains unclear, Sharma emphasizes. Ongoing and planned studies are investigating which patients with HSPC should receive a triplet regimen and which will receive a doublet regimen, Sharma concludes.