Janssen Ending Phase 3 Study of Apalutamide/Abiraterone Acetate in mCRPC

Janssen Pharmaceutical Companies of Johnson & Johnson announced that they are not perusing the regulatory submission for apalutamide (Erleada) and abiraterone acetate (Zytiga) as treatment of chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) after the combination was not found to show significant benefit over the control combination of prednisone and abiraterone acetate, according to a press release by the organization.¹

Apalutamide is an androgen receptor inhibitor that is currently approved for the treatment of patients with non-metastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. Abiraterone acetate is currently approved for the treatment of mCRPC.¹

The phase 3 ACIS Study (NCT02257736) found that the experimental combination did extended radiographic progression-free survival (rPFS), meeting the study’s primary endpoint, according to a presentation at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium. A follow-up analysis performed at 4.5 years found that the rPFS benefit persisted between the experimental and control combinations. However, there was no difference in overall survival (OS) between the two groups.

The phase 3 randomized study enrolled 983 participants. It had a primary endpoint of rPFS. Secondary outcomes included OS, time to chronic opioid use, time to initiation of cytotoxic chemotherapy, and time to pain progression.

During the study, participants were randomized 1:1 to received either 240 mg of apalutamide and 1000 mg of abiraterone acetate daily until disease progression, unacceptable toxicity, or the end of treatment, whichever comes first or 1000 mg of abiraterone acetate daily and 5 mg of prednisone twice daily. Patients also received a placebo to match the apalutamide once daily. Treatment was continued until disease progression, unacceptable toxicity, or the end of treatment.

In order to participate, patients must be male and 18 years old or older. Additionally, they must have metastatic disease with documented disease progression. Patients must small cell or neuroendocrine carcinoma of the prostate or known brain metastases are not eligible to participate.

At the median follow-up time of 25.7 months, the median rPFS for the experimental group was 22.6 months, which is 16.6 months in the comparative group. While OS was higher in the experimental arm, the difference was found to be not statistically significant. Additionally, time to PSA progression, chronic opioid use, initiation of cytotoxic chemotherapy, and pain progression did not differ statistically significantly between the two arms. Additionally, the safety profile of the experimental combination was consistent with prior drug experience, and no new safety concerns were raised. Grade 3 or 4 adverse events (AEs) were rereported in 63.3% of patients in the experimental arm and 56.2% in the control arm.²

“Safety results from ACIS were consistent with prior studies of ERLEADA and ZYTIGA plus prednisone, with no new safety signals observed. The study also generated valuable scientific outcomes and insights in subgroups of patients with luminal type in PAM50 test and tumors with average or high androgen receptor activity (molecular signatures of hormone sensitivity), which warrant further investigation,” said Kiran Patel, MD, vice president of clinical development, solid tumors at Janssen Research & Development, LLC, in a press release. “These data will be important in informing future programs in our pipeline, as we look to build upon our leadership and commitment in bringing transformational therapies to patients diagnosed with prostate cancer.”

_REFERENCE:

_{1.Janssen provides update on phase 3 ACIS Study in patients with metastatic castration-resistant prostate cancer treated with ERLEADA® (apalutamide) and ZYTIGA® (abiraterone acetate) Plus prednisone combination. News release. April 19, 2021. Accessed April 20, 2021. https://bit.ly/3n5Lp6n}

_{2. Rathkopf D, Efsathiou E, Attard G, et al. Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 39, 2021 (suppl 6; abstr 9) DOI: 10.1200/JCO.2021.39.6_suppl.9}