Higher Dose of Apalutamide for mCRPC and mCSPC Now Available in the United States

Neeraj Agarwal, MD

Apalutamide (Erleada), an FDA-approved androgen receptor (AR) inhibitor, is now available in United States in a 240 mg once-daily tablet, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).¹

“Studies have shown that taking many pills or a pill multiple times daily negatively affects patients’ treatment compliance and diminishes efficacy.² In this context, the availability of apalutamide as a single 240 mg tablet once daily will be very attractive to our patients with metastatic castration-sensitive prostate cancer or non-metastatic castration-resistant prostate cancer,” Neeraj Agarwal, MD, FASCO, professor of medicine, and a presidential endowed chair of cancer research, Huntsman Cancer Institute, University of Utah (NCI-CCC) told Targeted Oncology™.

The AR inhibitor was granted approval by the FDA for nmCRPC and mCSPC populations in 2019 based on results from the international, randomized, double-blind phase 3 TITAN trial (NCT02489318). At the time of the approval, apalutamide in combination with androgen deprivation therapy (ADT) elicited a 33% reduction in the risk of death compared with ADT alone (HR, 0.67; 95% CI, 0.51-0.89; P = .0053). The combination also demonstrated a 52% reduction in the risk of radiographic progression or death (HR, 0.48; 95% CI, 0.39-0.60; P < .0001).³

In 2021, the final analysis of the TITAN study confirmed the overall survival (OS) benefit of apalutamide, and demonstrated delayed castration resistance, health-related quality-of-life (HRQOL) maintenance, and tolerable safety in patients with mCSPC. The final analysis included 1052 patients who were randomized 1:1 to receive apalutamide plus ADT or ADT alone.⁴

At median follow-up of 44.0 months, the median OS was not reached in the apalutamide arm vs 39.8 months in the ADT-only arm, resulting in a 35% reduction in the risk of death (HR, 0.65; 95% CI, 0.53-0.79; P < .0001), in the intent-to-treat population. OS was also more favorable with the addition of apalutamide to ADT vs ADT alone across prespecified subgroups.

The risk of initiating cytotoxic chemotherapy was significantly reduced by 53% with apalutamide vs placebo. Results also favored the apalutamide arm in terms of the exploratory end points of prostate-specific antigen progression, and progression time from initial study randomization to 2nd disease progression or death.

Image Credit: © heitipaves [www.stock.adobe.com]

HRQOL was determined based on the Functional Assessment of Cancer Therapy – Prostate score. There was substantial improvement in HRQOL in the apalutamide arm compared with the ADT-only arm.

The duration of treatment in the apalutamide arm was 39.3 months compared with 20.2 months in the ADT-alone arm, and the overall incidence of treatment-emergent adverse events (TEAEs) was similar in both arms. The most common any-grade TEAEs in the apalutamide arm vs the ADT-alone arm were skin rash (24.4% vs 22.5%), fracture (6.1% vs 8.3%), and fall (4.6% vs 6.8%). In terms of grade 3 or 4 TEAEs, skin rash occurred in (7.6% vs 2.7%), fracture (2.9% vs 0.6%), and fall (0.7% vs 0.6%), respectively.

“Each person and their cancer are unique and, as such, there is no one-size-fits-all approach to treatment,” said Luca Dezzani, MD, vice president, medical affairs, solid tumor, Janssen Scientific Affairs, LLC, in a press release.¹ "The availability of 240 mg and 60 mg strength options of [apalutamide] demonstrates Janssen’s commitment to prostate cancer patients and provides prescribers flexibility in dosing and methods of administration to fit each patient’s unique needs.”

_REFERENCES:

_{1. ERLEADA® (apalutamide), first-and-only next-generation androgen receptor inhibitor with once-daily, single-tablet option, now available in the U.S. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. April 3, 2023. Accessed April 10, 2023. https://bit.ly/3zLjdNd}

_{2. Agarwal N, McQuarie K, Bjartell A, et al. Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019;20(11):1518-1530. doi: 10.1016/S1470-2045(19)30620-5.}

_{3. FDA approves apalutamide for metastatic castration-sensitive prostate cancer. FDA.gov. September 17, 2019, Accessed April 10, 2023. https://bit.ly/2lVOeve}

_{4. Chi K, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase 3 TITAN study. J Clin Oncol. 2021;39(20): 2294-2303. doi: 10.1200/JCO.20.03488}