Apalutamide Now Also Approved for Metastatic Prostate Cancer

Zosia Chustecka


September 19, 2019

Last year, apalutamide (Erleada, Janssen) became the first drug to be approved in the United States for use in the treatment of nonmetastatic, castration-resistant prostate cancer. The approval marked the first time that the US Food and Drug Administration used metastasis-free survival as the primary endpoint in its decision making.

Apalutamide has now also been approved for use in metastatic castration-sensitive prostate cancer (mCSPC).

This approval is based on the more traditional primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS). The findings are from the phase 3 TITAN study.

The results from this study were presented at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) and were simultaneously published in the New England Journal of Medicine, as reported by Medscape Medical News at the time.

"The rationale behind the TITAN study was [the idea that] direct inhibition of the androgen receptor by apalutamide may provide a more complete reduction of androgen signaling than androgen deprivation therapy (ADT) alone, leading to improved clinical outcomes," explained study author Kim Chi, MD, medical oncologist at BC Cancer Agency in Vancouver, Canada.

Apalutamide plus ADT significantly extended OS compared to placebo plus ADT, with a 33% reduction in the risk for death (hazard ratio [HR], 0.67; P = .0053). In addition, rPFS was significantly improved compared to placebo plus ADT, with a 52% lower risk for radiographic progression or death (HR, 0.48; P < .0001).

The 2-year OS rates, after a median follow-up of 22.7 months, were 84% for patients who received apalutamide plus ADT compared to 78% for those who received placebo plus ADT.

"Prostate cancer is more difficult to treat once it spreads, and for patients with castration-sensitive disease, it is clear that androgen deprivation therapy (ADT) alone, is often not enough," Chi said in a press release about the new approval.

"Results from the TITAN study showed that, regardless of the extent of disease, patients with metastatic castration-sensitive prostate cancer have the potential to benefit from treatment with apalutamide in addition to ADT," Chi added.

Commenting on the new data at the ASCO meeting, discussant Michael Carducci, MD, AEGON professor in prostate cancer research at Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, said that the TITAN study confirms that the current standard for mCSPC should be a combination of ADT and chemotherapy or an androgen receptor inhibitor, such as enzalutamide (Xtandi, Astellas) and abiraterone (Zytiga, Janssen) and now also apalutamide.

The most common adverse reactions (≥10%) that occurred more frequently in apalutamide-treated patients (≥2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.

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