enzalutamide (XTANDI®, Astellas Pharma Inc.) for patients with metastatic castration-sensitive prostate cancer (mCSPC).

[Darryl]

On December 16, 2019, the Food and Drug Administration approved enzalutamide (XTANDI®, Astellas Pharma Inc.) for patients with metastatic castration-sensitive prostate cancer (mCSPC).

FDA previously approved enzalutamide for patients with castration-resistant prostate cancer.

Efficacy was investigated in ARCHES (NCT02677896), a trial enrolling 1150 patients with mCSPC randomized (1:1) to receive either enzalutamide orally 160 mg once daily (N=574) or placebo orally once daily (N=576). All patients received a GnRH analog or had a prior bilateral orchiectomy.

The main efficacy outcome measure was radiographic progression-free survival (rPFS). Based on blinded independent central review, rPFS was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after drug discontinuation. Radiographic disease progression was defined by identification of 2 or more new bone lesions on a bone scan with confirmation (Prostate Cancer Working Group 2 criteria) and/or progression in soft tissue disease. Time to new antineoplastic therapy was an additional endpoint.

Median rPFS was not reached (NR) in the enzalutamide arm compared to 19.4 months (95% CI: 16.6, NR) in the placebo arm (HR 0.39; 95% CI: 0.30, 0.50; p<0.0001). A statistically significant improvement was also reported on the enzalutamide arm compared to placebo in time to initiation of a new antineoplastic therapy (HR 0.28; 95% CI: 0.20, 0.40; p<0.0001). Overall survival (OS) data were not mature at the time of rPFS analysis.

The most common adverse reactions (≥ 5%) that occurred more frequently (≥ 2% over placebo) in enzalutamide-treated patients in ARCHES were hot flush, asthenia/fatigue, hypertension, fractures, and musculoskeletal pain.

The recommended dose is 160 mg (four 40 mg capsules) administered orally once daily, with or without food.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. This application was approved two weeks prior to the FDA goal date.

Enzalutamide was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

[Tall_Allen]

What is interesting is that the FDA accepted radiographic progression-free survival as a surrogate endpoint for mHSPC. The other approved medicines (Zytiga, Erleada and Taxotere) were required to prove increases in overall survival. Nubiqa, Erleada and Xtandi were approved for non-metastatic CRPC based on delay of the appearance of the first metastasis.

[Darryl Partner in reply to Tall_Allen]

Yes, I noticed and wondered about that, too. I hope to get a reply from their Medical Director.

[Pierreb]

Hi Guys, Has there been any comparison of XTANDI vs Zytiga in mHSPC? Or is there a study currently ongoing at the moment?

[Tall_Allen in reply to Pierreb]

STAMPEDE has an ongoing trial of that.

[Pierreb in reply to Tall_Allen]

Thank you Allen!!!! I've heard of that one before but I'm a bit clueless when it comes to actually knowing or understanding a lot of that stuff. I am grateful for you and all the other guys on this site that know / understand this stuff. Thank you Allen.

[MateoBeach]

Seems only natural that as treatments are testes in earlier disease stages that surrogate endpoints be used for evaluation and make approval possible earlier than for OS. Even though the surrogate may reflect a delay of progression while not affecting survival. The question of burning your matches early or saving them for a later day remains.

I am happy to see this approval and more choices made available.

[monte1111]

Believe I would be considered mCSPC and have been on Xtandi 28 months. (After 8 cycles chemo, plus constant lupron) PSA from 59.9 to 0.1 Alk Phosphatase from a little over 200 to 74. Extensive bone mets stable. No new mets. (July 2019) Guess my doctor jumped the gun on this one, but it has worked well so far. Like any of these drugs, works for some, doesn't work for some. And then quits working.

[Paul_Henderson]

I just started Xtandi this week - cautiously optimistic on side effects - definitely an upswing in hot flashes but I've been on Lupron for more than 6 years so I've sort of adjusted, or maybe just learned to ignore many of them. Just hoping I get a good run on it.

[Bebby1]

My husband is grateful to have been able to use this drug for the past 6 months, however he has become resistant and now meets criteria for a new Trial

Good luck to all those who are eligible as many others have had success in fighting this beast with the drug