Xtandi Shows Superior Survival Outcomes to Abiraterone in Treatment of Metastatic Castration-Resistant Prostate Cancer

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A retrospective, multicenter cohort study found that Xtandi (enzalutamide) achieved small but statistically significant improvements in survival and responses compared with abiraterone acetate in the treatment of metastatic castration-resistant prostate cancer (mCRPC).¹ The investigators noted that although both abiraterone acetate and Xtandi have differing mechanisms of action, toxicities, and costs, both are effective and widely used in the treatment of mCRPC, despite having relative benefits and risks that are yet to be fully understood.

“Each agent has been extensively studied in separate clinical trials including the pivotal trials leading to approval, but to our knowledge, they have not been compared in large-scale, head-to-head trials,” the study authors wrote. “Observational studies comparing the 2 agents have been limited as to sample size, study design, length of follow-up, lack of information on key variables such as castration resistance, or a combination of these factors.”¹

Xtandi has multiple approvals in prostate cancer, including its most recent in November 2023 for the treatment of nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis. To date, more than 300,000 men in the United States have been prescribed Xtandi, which has demonstrated improved overall survival (OS) in patients with mCRPC, nmCSPC, and metastatic castration-sensitive prostate cancer.²

The current study compared Xtandi with abiraterone acetate to evaluate outcomes in patients with mCRPC. Data were pulled from the VA healthcare system for patients with mCRPC who began treatment with Xtandi or abiraterone acetate between January 1, 2014, and October 30, 2022. A total of 5779 patients were included in the analysis, who had a median age of 74.42 years (IQR, 68.94-82.14 years), with median follow-up conducted between 38 and 60 months.

Investigators incorporated inverse probability of treatment weighting to balance baseline characteristics among patients in the trial to analyze restricted mean survival time (RMST) differences in OS, prostate cancer–specific survival (PCS), time to next treatment switching or death (TTS), and time to prostate-specific antigen (PSA) response (TTR) at different time points after treatment initiation.

The results showed that patients administered Xtandi had an average OS longer than patients initiating abiraterone acetate. RMST in the Xtandi cohort was 24.29 months (95% CI, 23.58-24.99 months) compared with 23.38 months (95% CI, 22.85-23.92 months) in the abiraterone acetate cohort, which translates to a difference in RMST of 0.90 months (95% CI, 0.02-1.79 months) at the four-year mark. RMST at four years was 1.95 months (95% CI, 0.92-2.99 months) longer for TTS in the Xtandi cohort and 3.57 months (95% CI, 1.76-5.38 months) shorter for TTR in the Xtandi cohort. RMST at two years for PCS was 0.48 months (95% CI, 0.01-0.95 months) longer in the Xtandi cohort.

A subgroup analysis showed that initiation of treatment with Xtandi was linked to longer RMST in OS among patients who did not receive prior treatment with docetaxel (1.14 months; 95% CI, 0.19-2.10 months) and in patients with PSA doubling time of three months or more (2.23 months; 95% CI, 0.81-3.66 months), but not among those previously administered docetaxel (−0.25 months; 95% CI, −2.59 to 2.09 months) or who had PSA doubling time of fewer than three months (0.05 months; 95% CI, −1.05 to 1.15 months).

“In this cohort study of patients with mCRPC, we found that initial enzalutamide treatment, in general, was associated with more favorable outcomes than initial abiraterone acetate treatment,” the study authors concluded. “The improvements were more prominent in short-term outcomes, including TTS and TTR, and in patient subgroups with less aggressive prostate cancer (without prior docetaxel treatment or with PSA doubling time ≥3 months). The findings of this large-scale observational study with robust follow-up and rigorous methods may provide guidance for making well-informed decisions about mCRPC treatment strategies.”¹

References

1. La J, Wang L, Corrigan JK, et al. Abiraterone or Enzalutamide for Patients With Metastatic Castration-Resistant Prostate Cancer. JAMA Netw Open. 2024;7(8):e2428444. doi:10.1001/jamanetworkopen.2024.28444

2. Pfizer and Astellas' XTANDI® Approved by U.S. FDA in Earlier Prostate Cancer Treatment Setting. Astellas Pharma Inc. News release. November 17, 2023. Accessed August 19, 2024. https://www.astellas.com/en/news/28626