Apalutamide Demonstrates Real-World OS Benefit vs Enzalutamide in mCSPC

Neal Shore, MD, FACS

Data from a real-world study showed that treatment with apalutamide (Erleada) led to a statistically significant improvement in overall survival (OS) at 24 months compared with enzalutamide (Xtandi) in patients with metastatic castration-sensitive prostate cancer mCSPC).^1,2

Findings presented in a poster at the 6th European Congress of Oncology Pharmacy showed that patients treated with apalutamide (n = 1810) experienced a 24-month OS rate of 87.6% compared with 84.6% for those given enzalutamide (n = 1909; HR, 0.77; 95% CI, 0.62-0.96; P < .019).² The 48-month OS rates were 75.6% and 68.1% for apalutamide and enzalutamide, respectively.

“This real-world evidence showed a statistically significant and clinically meaningful improvement in [OS] with apalutamide over enzalutamide in patients with mCSPC at 24 months,” study investigator Neal Shore, MD, FACS, steering committee chair and medical director at the Carolina Urologic Research Center, stated in a news release.¹ “Head-to-head, randomized and controlled phase 3 studies have been the gold standard for comparing the effectiveness of oncology medicines; however, prospective androgen receptor pathway inhibitor [ARPI] comparator trials have not been conducted. This real-world study is provocative as the comprehensive data and rigorous methodology used in this study offers real-world insights on OS, which can provide prescribers with information to consider when choosing an ARPI.”

In September 2019, the FDA approved apalutamide for the treatment of patients with mCSPC, based on data from the phase 3 TITAN trial (NCT02489318).³ Those results showed that at a median follow-up of 22.7 months, apalutamide plus androgen deprivation therapy (ADT) reduced the risk of death by 33% compared with placebo plus ADT (HR, 0.67; 95% CI, 0.51-0.89; P = .005); at a median follow-up of 44 months, the risk of death was reduced by 35% for apalutamide plus ADT vs placebo plus ADT (HR, 0.65; 95% CI, 0.53-0.79; P < .0001).¹ In the news release, Johnson & Johnson noted that the 24-month OS rate observed for apalutamide in the real-world study was consistent with the 24-month OS rate for the experimental arm in TITAN (82.4%).

In December 2019, the FDA also approved enzalutamide for the treatment of patients with mCSPC.⁴ This decision was supported by findings from the phase 3 ARCHES trial (NCT02677896), where treatment with enzalutamide plus ADT led to a median radiographic progression-free survival that was not reached vs 19.4 months for placebo (HR, 0.39; 95% CI, 0.30-0.50; P < .0001).

Since no prospective trials have been conducting comparing apalutamide and enzalutamide in the treatment of patients with mCSPC, investigators of the real-world study aimed to evaluate the 24-month OS rates for patients treated with the two agents.²

Using electronic databases, investigators identified patients with mCSPC who initiated treatment with apalutamide or enzalutamide between December 16, 2018, and December 31, 2023. Notably, concurrent use of ADT was not required for inclusion in either arm.

The primary end point of the real-world study was the proportion of patients alive at 24 months following the initiation of one of the ARPIs. Study authors noted that baseline characteristics were generally well balanced between the two arms.

The median follow-up was 20.1 months for both the apalutamide and enzalutamide arms. The median duration of continuous ARPI use from the index date was 6.9 months in the apalutamide arm vs 6.4 months in the enzalutamide arm.

Additional data showed that when using all available follow-up, the OS benefit associated with apalutamide was consistent with the 24-month data (HR, 0.77; 95% CI, 0.64-0.93; nominal P = .008).

Shore and coauthors noted that the real-world study was potentially limited by miscoding or misclassification in electronic records or claims that could add information or selection biases. Additionally, they explained that the database represents patients treated in community urologic practices, which may not represent the full population of patients with mCSPC in the United States. Furthermore, in prospective clinical trials, OS is assessed following a prespecified number of events, whereas the real-world study examined OS at the prespecified time point of 24 months.

“Since [apalutamide’s] approval, multiple ARPIs have been introduced, but no one has directly compared their effectiveness on a large scale—until now,” Luca Dezzani, MD, U.S. vice president of Medical Affairs, Solid Tumors, at Johnson & Johnson Innovative Medicine, added in a news release.¹ “With a decade-plus legacy in prostate cancer, we have pushed the field further with this additional evidence showing an OS benefit with [apalutamide], which is a patient-centric option taken as just one pill, once daily.”

References

1. Erleada (apalutamide) demonstrates statistically significant and clinically meaningful improvement in overall survival compared to enzalutamide in patients with metastatic castration-sensitive prostate cancer. News release. Johnson & Johnson. October 2, 2024. Accessed October 8, 2024. https://www.investor.jnj.com/news/news-details/2024/ERLEADA-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer/default.aspx
2. Bilen MA, Lowentritt B, Khilfeh I, et al. Real-world head-to-head analysis of overall survival in patients with metastatic castration-sensitive prostate cancer initiated on apalutamide versus enzalutamide in the United States. Presented at: 6th European Congress of Oncology Pharmacy; October 2-4, 2024; Lisbon, Portugal. Abstract P31.
3. FDA approves apalutamide for metastatic castration-sensitive prostate cancer. FDA. September 17, 2019. Accessed October 8, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-apalutamide-metastatic-castration-sensitive-prostate-cancer
4. FDA approves enzalutamide for metastatic castration-sensitive prostate cancer. FDA. December 16, 2019. Accessed October 8, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-enzalutamide-metastatic-castration-sensitive-prostate-cancer