ASCO 2019: Dr. Tagawa Highlights Key Prostate Cancer Data

Scott T. Tagawa, MD, Richard A. Stratton Associate Professor in Hematology and Oncology, associate professor of clinical medicine & urology at Weill Cornell Medicine, associate attending physician, NewYork-Presbyterian—Weill Cornell Medical Center, discusses key data in prostate cancer presented at the 2019 ASCO Annual Meeting.

In the phase III ENZAMET trial, 80% of men with metastatic hormone-sensitive prostate cancer (mHSPC) treated with enzalutamide (Xtandi) plus the standard of care were alive at 3 years compared with 72% of patients treated with a different non-steroidal anti-androgen (NSAA) plus standard of care (HR, 0.67; 95% CI, 0.52-0.86; P = .002). This is the first trial in this space to report positive overall survival (OS) data for the use of enzalutamide and testosterone suppression.

The time until clinical prostate-specific antigen (PSA) rise and clinical progression or death was also significantly increased with enzalutamide compared with other NSAAs (HR, 0.39; 95% CI, 0.33-0.47; P <.001). Tagawa said these data are significant because they not only add another viable option to the mHSPC treatment paradigm, they also support the hypothesis that these drugs work better upfront.

Based on the results of the phase III TITAN trial, apalutamide (Erleada) has emerged as a promising option for patients with metastatic castration-sensitive prostate cancer. The study showed that adding apalutamide to androgen deprivation therapy (ADT) reduced the risk of death by 33% compared with ADT alone. At a median follow-up of 22.7 months, the 2-year OS rate was 82.4% compared with 73.5% in the control arm (HR, 0.67; 95% CI, 0.51-0.89; P = .005).

A third androgen receptor (AR) antagonist, darolutamide, is also making headway, particularly in the nonmetastatic castration-resistant space. Updated data from the phase III ARAMIS trial presented at the 2019 ASCO Annual Meeting focused on patient-reported outcomes and health-related quality of life. Researchers showed that the addition of darolutamide to ADT significantly delayed PSA progression compared with placebo. Moreover, the AR inhibitor reduced pain progression by approximately 40% compared with placebo.

Tagawa notes that darolutamide has a similar mechanism of action to enzalutamide and apalutamide. Though, darolutamide could hold an advantage in terms of tolerability. This will have to be confirmed with further data.

Additional abstracts of interest include those with olaparib (Lynparza), which is building on the potential for PARP inhibition in patients with mCRPC who harbor DNA repair defects. Tagawa says that patients with BRCA1/2 mutations tend to do worse with standard therapy.

Switching gears to metastatic urothelial carcinoma, Tagawa noted his excitement for enfortumab vedotin, a novel therapeutic agent that induced a 44% response rate in patients with locally advanced or metastatic disease. Median OS with the drug was 11.7 months, according to phase II data presented at the 2019 ASCO Annual Meeting.