ASCO GU 2017: Phase Ib study of apalutamide (APA) with abiraterone acetate (AA) and prednisone (P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Update on safety and efficacy.

Orlando, Florida USA (UroToday.com) Posadas et al. presented work detailing the results of a Phase 1B study of apalutamide (APA) with abiraterone (AA) + prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). APA is a novel androgen receptor (AR) antagonist that targets the AR-ligand binding domain with a particularly high affinity. Abiraterone is a drug that disrupts the androgen production axis by inhibiting CYP17, thereby blocking adrenal production of androgens. It is approved for treatment of mCRPC and is already in widespread use.

This trial was conducted to evaluate the potential pharmacokinetic interactions between APA and AA, as well as to evaluate the antitumor activity of combination therapy in mCRPC patients. 57 patients were enrolled in this trial, supported by Janssen Pharmaceuticals.

Patients who received no prior therapy with AA or enzalutamide (n = 18) demonstrated the most favorable response to combination therapy, with 67% achieving maximal PSA response to therapy. Furthermore, these patients also stayed on study longer than patients who had previously been exposed to AA or enzalutamide.

Overall, drug-related adverse events (AE) occurred in almost all (91%) patients, though only 21% of these were Grade 3 or 4. Still, this is a significant AE profile and likely related to the additive toxicities of the two investigational drugs. Most prevalent were liver enzyme abnormalities, GI toxicity related to APA, and fatigue.

The authors conclude that combination therapy with AA and APA does have antitumor activity as assessed by PSA response, and that the safety profile falls within expected range. Although all patients appeared to demonstrate a response, those who had no previous exposure to AR-directed therapies had the greatest response. Furthermore, they did not find a significant PK interaction between the drugs. Given these results, an ongoing Phase 3 trial is underway; and results should be available by next year.

Combination therapy disrupting the androgen production/response axis may prove an important weapon in the battle against mCRPC. The stronger the disruption, the better the response most patients are likely to have. Unfortunately, this strategy also probably equates to more toxicity; and AEs may need to be more thoroughly vetted in order to maximize the risk/benefit ratio for treatment.

First Author: Edwin Posadas; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA

Written By: Shreyas Joshi, MD, Fox Chase Cancer Center

at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA

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