Apalutamide associated with improved 2-year survival vs enzalutamide in mCSPC

Apalutamide (Erleada) was found to provide a significant improvement in overall survival (OS) at 24 months compared with enzalutamide (Xtandi) in the treatment of androgen receptor pathway inhibitor (ARPI)-naïve patients with metastatic castration-sensitive prostate cancer (mCSPC), according to data from a head-to-head retrospective analysis presented at the 6th European Congress of Oncology Pharmacy in Lisbon, Portugal.¹

Neal Shore, MD, FACS

"This real-world evidence showed a statistically significant and clinically meaningful improvement in survival with apalutamide over enzalutamide in patients with mCSPC at 24 months," said lead author Neal Shore, MD, FACS, Steering Committee Chair and Medical Director at the Carolina Urologic Research Center, in a news release on the findings.² "Head-to-head, randomized and controlled phase 3 studies have been the gold standard for comparing the effectiveness of oncology medicines, however, prospective 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 overall survival which can provide prescribers with information to consider when choosing an ARPI."

Data from the study showed that at the 24-month time point, patients who received apalutamide had a 23% reduction in the risk of death compared with patients who initiated enzalutamide (HR, 0.77; 95% CI, 0.62-0.96; P = .019). This finding was consistent when evaluating OS using all follow-up (HR, 0.77; 95% CI, 0.64-0.93; P = .008).

In total, 87.6% of patients in the apalutamide arm were alive at 24 months. According to the news release, this finding is consistent with that observed in the phase 3 TITAN trial (NCT02489318), in which 82.4% of patients were alive at 24-month follow-up.

Overall, the TITAN trial demonstrated that the combination of apalutamide and androgen deprivation therapy (ADT) significantly extended overall survival vs ADT alone at both the median primary analysis follow-up of 22.7 months (HR 0.67; 95% CI, 0.51-0.89; P = .005) and at the median final analysis follow-up of 44 months (HR 0.65; 95% CI, 0.53-0.79; P < .0001).³

"[Apalutamide] is the only ARPI to demonstrate a survival benefit as early as 22 months, as seen in the TITAN study. Since [apalutamide]'s approval, multiple ARPIs have been introduced, but no one has directly compared their effectiveness on a large scale—until now," said Luca Dezzani, MD, U.S. Vice President, Medical Affairs, Solid Tumors at Johnson & Johnson Innovative Medicine, in the news release.² "With a decade-plus legacy in prostate cancer, we have pushed the field further with this additional evidence showing an overall survival benefit with [apalutamide], which is a patient-centric option taken as just 1 pill, once daily."

In total, the current study included data from 3719 patients with mCSPC who had not received a prior ARPI. Of those, 1810 initiated treatment with apalutamide, and 1909 initiated treatment with enzalutamide. Data were obtained from PPS Analytics and Komodo, which are both large, deidentified linked health care databases.

The average age of patients was 73 years. Among all patients, approximately 60% were White and 23% were Black. Further, about 72% had bone metastasis, 49% had nodal metastasis, and 20% had visceral metastasis. Approximately 81% used ADT at the time of index, which was defined as the first prescription date of either apalutamide or enzalutamide.

According to the authors, population characteristics were similar between both arms.

The primary objective of the study was to compare 24-month OS between patients who received apalutamide and patients who received enzalutamide.

Some limitations of the current study include the potential for miscoding or missing information in the data sources used and an assessment point of 24 months. According to the news release, “longer-term studies are needed to fully evaluate the therapeutic effects of these treatments.”²

References

1. Shore N, 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. Lisbon, Portugal. October 2-4, 2024. Abstract P31. https://ecop.events/wp-content/uploads/2024/09/Clinical_evaluation.pdf

2. 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. Published online and accessed October 2, 2024. https://www.prnewswire.com/news-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer-302265567.html

3. Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: Final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. doi:10.1200/JCO.20.03488