Apalutamide sees greater PSA response compared with enzalutamide for patients with mCSPC

Benjamin H. Lowentritt, MD, FACS

Benjamin H. Lowentritt, MD, FACS

Patients receiving the metastatic castration-sensitive prostate cancer treatment apalutamide (Erleada) achieved a more significant prostate-specific antigen (PSA) reduction from baseline of 90% (PSA90) when compared enzalutamide (Xtandi), investigators reported at the 2022 Genitourinary Cancers Symposium in San Francisco, California.1

Patients treated with apalutamide (n = 174) achieved a PSA90 response at a 70.4% rate compared with 62.5% of patients who received enzalutamide (n = 177) at the end of the 12-month follow-up (HR, 1.49; 95% CI, 1.05-2.11; P = .024). The median time to PSA90 response was 3.13 months and 5.20 months in the apalutamide and enzalutamide groups, respectively. Weighted Kaplan-Meier analysis was used to assess the proportion of patients who achieved a PSA90 response and to assess the median to PSA90.

“The clinical implications of these observations warrant further consideration given existing evidence on the association between attainment of rapid, deep, and durable PSA response with survival-related end points in patients treated with these medications,” study authors wrote.

Both apalutamide and enzalutamide are next-generation androgen receptor inhibitors. Enzalutamide was approved by the FDA on December 16, 2019, and apalutamide was approved in this indication on September 17, 2019.

The index date of the study was defined as the first dispensation of apalutamide or enzalutamide following the approval date of enzalutamide. Patients were assigned to mutually exclusive treatment cohorts based on the first dispensation of apalutamide or enzalutamide. The observation period went from the index date to either index treatment discontinuation, initiation of a different next-generation androgen inhibitor, the use of radiopharmaceuticals, the end of clinical activity, or the end of data availability, whichever occurred first.

In terms of statistical analysis methods, inverse probability of treatment weighting based on propensity score (PS) was used to account for the differences in baseline characteristics in the apalutamide and enzalutamide groups. PS was determined by a logistic regression model for apalutamide or enzalutamide treatment assignments with the baseline characteristics of age, race, index year, androgen deprivation therapy (ADT) use of 6 months or more, first-generation antiandrogen use, most recent PSA level, most recent testosterone level, Gleason score, and time between metastasis and the index date.

Investigators wanted to compare the proportion of patients with mCSPC newly treated with apalutamide versus enzalutamide who achieved a PSA90 response at 6 months and beyond. The data used in the study was sourced from Precision Point Specialty Analytics and was collected as part of routine clinical care from 69 United States urology clinics from February 1, 2017, to March 5, 2021. The data was de-identified and was Health Insurance Portability and Accountability Act compliant.

To be included in the study, patients had to be at least 18 on the index date, have at least 1 medication dispensation for apalutamide or enzalutamide, and have at least 12 months of clinical activity prior to the index date. Eligible patients also needed to have evidence of metastatic prostate cancer, defined by the presence of bone, nodal, visceral metastasis prior to or on the index date. A minimum of 1 PSA test during the 13 weeks prior to and including the index date was required.

Patients were excluded from the study if they had prior use of a radiopharmaceutical or a next-generation androgen inhibitor before the index date, or the use of 2 or more next-generation androgen inhibitors. If patients displayed evidence of castration resistance prior to or on the index date, they were not included in the study.

Baseline patient characteristics were evaluated in the 12 months preceding the index date. In the weighted apalutamide group, the median age was 76.0 compared with 75.0 in the enzalutamide cohort. Most patients in both groups were White (71.0% vs 70.5%, respectively), had an index date from 2019-2020 (77.2% vs 77.1%, respectively), and reported prior ADT use (91.4% vs 91.2%, respectively). The mean baseline PSA level was 18.4 ng/mL in the apalutamide cohort compared with 18.3 ng/mL.

PSA testing frequency was similar between the 2 cohorts; 73.6% and 69.5% of patients had a post-index PSA measurement by 6 months in the apalutamide and enzalutamide groups, respectively. A median of 3.8 PSA tests were done per year in the apalutamide cohort compared 3.3 in the enzalutamide cohort. Most patients in both groups had a PSA test every 6 months on average (71.2% vs 67.8%, respectively).

At 6 months follow-up, 69.3% of the apalutamide group achieved a PSA90 response versus 55.6% in the enzalutamide group (HR 1.56; 95% CI, 1.09-2.22; P = .014). Apalutamide also outperformed enzalutamide in terms of PSA90 response at the 9-month mark (70.4% vs 62.5%; HR, 1.49; 95% CI, 1.05-2.11; P = .024).

The investigators noted that the study was limited because some of the clinical data used could contain inaccuracies or omissions, and the data did not capture any clinical services obtained outside of the urology practice. The study didn’t address if the findings represent a clinically meaningful difference or if they translate into differences in longer-term outcomes. Additionally, the database that was used represented the community urology perspective and may not necessarily be representative of the entire United States population of patients with mCSPC.


  1. Lowentritt B, Pilon D, Khilfeh I, et al. Attainment of early, deep prostate-specific antigen response in metastatic castration-sensitive prostate cancer: A comparison of patients initiated on apalutamide or enzalutamide. J Clin Oncol. 2022;40(suppl 6):43. doi:10.1200/JCO.2022.40.6_suppl.043

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