FDA Updates Enzalutamide Label in mCRPC


The FDA has updated the label for enzalutamide in metastatic castration-resistant prostate cancer to include new data from the phase II TERRAIN study.

Steven Benner, MD

Steven Benner, MD

Steven Benner, MD

The FDA has updated the label for enzalutamide (Xtandi) in metastatic castration-resistant prostate cancer (mCRPC) to include new data from the phase II TERRAIN study, according to the codevelopers of the androgen receptor inhibitor, Astellas and Pfizer.

In the trial, enzalutamide reduced the risk of radiographic progression or death by 40% compared with bicalutamide. The median radiographic progression-free survival (rPFS) was improved by 6.1 months with enzalutamide.

“The addition of data from the TERRAIN trial continues to build the body of evidence that demonstrates the clinical impact Xtandi can have for patients living with metastatic CRPC,” Steven Benner, MD, senior vice president, therapeutic area head for oncology development, Astellas, said in a statement. “Advances in scientific knowledge as seen through clinical trials like TERRAIN would not be possible without the participation of hundreds of patients, family members and clinical investigators, and we thank them for their valuable contributions.”

The Phase II TERRAIN trial randomized 375 chemotherapy-naïve patients with mCRPC in a 1:1 ratio to receive enzalutamide at 160 mg orally once daily or bicalutamide at 50 mg once daily.

The median radiographic progression-free survival was 19.5 months with enzalutamide compared with 13.4 months with bicalutamide (HR, 0.60; 95% CI, 0.43-0.83).

The safety data for enzalutamide was comparable to results reported from previous enzalutamide studies. The most common all-grade adverse events (AEs) with enzalutamide included asthenic conditions, back pain, musculoskeletal pain, hot flush, hypertension, diarrhea, upper respiratory tract infection, and weight loss.

Grade 3/4 AEs occurred in 38.8% and 37.6% of the enzalutamide and bicalutamide arms, respectively. Although most grade ≥3 AEs occurred at similar rates between the arms, there were a few exceptions: hypertension (7.1% in the enzalutamide arm vs 4.4% in the bicalutamide arm), diarrhea (0% vs 1.1%), and back pain (2.7% vs 1.6%). Seizures occurred in 2 patients in the enzalutamide group and 1 patient in the bicalutamide group.

The FDA initially approved enzalutamide in August 2012 for use in patients with mCRPC previously treated with docetaxel and hormonal therapy. The approval was based largely on data from the phase III AFFIRM study in which 1199 men with mCRPC were randomized in a 2:1 ratio to receive enzalutamide or placebo. The median overall survival (OS) was 18.4 months with enzalutamide versus 13.6 months in the control arm (HR, 0.63; 95% CI, 0.53-0.75; P <.001).

In September 2014, the FDA expanded the approval of enzalutamide to include the treatment of men with chemotherapy-naïve mCRPC, based on survival data from the phase III PREVAIL trial.

In the phase III study, 1717 men with a median age of 71 years received treatment with enzalutamide (n = 872) or placebo (n = 845). Enzalutamide was administered at 160 mg daily. An interim analysis was conducted following 540 deaths, which demonstrated a statistically significant advantage for enzalutamide for both OS and rPFS. At that point, the study was halted and men in the placebo arm were allowed to cross over to receive enzalutamide.

The median OS was 32.4 months with enzalutamide versus 30.2 months with placebo (HR = 0.71; P <.0001). The median rPFS was not yet reached in the enzalutamide arm compared with 3.9 months with placebo (HR = 0.19; P <.0001). The overall response rate was 58.8% versus 5%, for enzalutamide versus placebo, respectively (P <.0001).

“We are pleased with the FDA's decision to update the Xtandi label with these data from the first and largest comparative trial that demonstrated safety and efficacy of enzalutamide compared to bicalutamide,” Mohammad Hirmand, MD, interim chief medical officer at Medivation, which is now part of Pfizer, said in a statement. “We believe these data will help physicians better understand the differences between enzalutamide and bicalutamide for their patients living with metastatic CRPC.”

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