Johnson & Johnson Erlead (apatamide) + Zytiga (abiraterone acetate) Phase-3 clinical success!

Johnson & Johnson Erlead + Zytiga Phase-3 clinical success!   Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced Erleada at the American Society of Clinical Oncology Symposium on Genitourinary Cancer (ASCO-GU 2021) held on February 11, 2021. Erleada (generic name: apalutamide) Amine) combined with Zytiga (generic name: abiraterone acetate, abiraterone acetate) in the treatment of prostate cancer phase 3 ACIS study results.

The data showed that the study reached the primary endpoint: in patients with metastatic castration-resistant prostate cancer (mCRPC) who had not previously received chemotherapy (naïve chemotherapy) and were receiving androgen deprivation therapy (ADT), compared with placebo + Compared with the Zytiga+prednisone treatment group (control group), the Erleada+Zytiga+prednisone treatment group (combination group) significantly improved radiological progression-free survival (rPFS) and reduced the risk of radiological progression or death by 31%.

ACIS is a randomized, double-blind, placebo-controlled Phase 3 study, carried out in 982 patients receiving ADT and chemotherapy-naïve mCRPC. In the study, these patients were randomly assigned to receive the Erleada+Zytiga+prednisone regimen (combination group) or placebo+Zytiga+prednisone regimen (control group). The primary endpoint of the study is radiological progression-free survival (rPFS), and secondary endpoints include overall survival (OS), the time to start long-term opioids, the time to start cytotoxic chemotherapy, and the time to pain progression.

The preliminary efficacy analysis showed that the median rPFS of the combination group was extended by 6 months compared with the control group (22.6 vs 16.6 months; HR=0.69[95%CI:0.58-0.83]; p<0.0001).

The HR for radiological progress or death assessed by the blinded independent central review (BICR) was 0.864 [95%CI: 0.718–1.040]. According to the latest analysis with a median follow-up of 54.8 months, compared with the control group, the risk of radiological progression or death in the combination group was reduced by 30% (median rPFS: 24 months vs 16.6 months; HR=0.70 [95%CI :0.60-0.83]).

In terms of secondary endpoints (including overall survival [OS], time to start cytotoxic chemotherapy, time to start long-term use of opioids, and time to pain progression), there was no statistically significant difference between the combination group and the control group.

The entire ACIS study population is heterogeneous in terms of androgen receptor (AR) resistance and sensitivity markers. Data from the pre-specified analysis showed that patients with visceral metastases, PAM50 test of the lumen type, and AR activity of average or high (molecular characteristics of hormone sensitivity) may be from Erleada+Zytiga+preny The clinical benefit of pine combination therapy is as revealed by the results of rPFS and OS in these subgroups of patients.

The safety analysis is consistent with Erleada’s previous research, and no new safety signals have been observed. 63.3% of the combined group and 56.2% of the control group had adverse events (TEAEs) that occurred during grade 3/4 treatment. Grade 3/4 TEAEs that occur more frequently in the combination group and the control group include:

• Fatigue (4.7% vs 3.9%),
• Hypertension (20.6% vs 12.5%),
• Falls (3.3% vs 0.6%),
• Skin rash (4.5% vs 0.4%),
• Heart disease (9% vs 5.7%),
• Fractures and osteoporosis (4.1% vs 1.4%)
• Seizures (0.2% vs 0%).

According to the cancer treatment-prostate function assessment (FACT-P Total), the quality of life of the combination group and the treatment group is comparable.

Prostate cancer (Image source: hopkinsmedicine.org)

Dana Rathkopf, chief investigator of the ACIS study and medical oncologist at Memorial Sloan Kettering Cancer Center, said: “Data from the ACIS study shows that when treating patients with metastatic castration-resistant prostate (mCRPC), Erleada + Zytiga + Penny There was a significant increase in rPFS in the pine combination therapy group. In this study, the insights on the differences in the benefits of specific patient subgroups of combination therapy deserve further evaluation.

Craig Tendler, MD, Vice President of Oncology Development and Global Medical Affairs, Janssen Research and Development, said: “The results of the ACIS study demonstrate the potential role of combination therapy in mCRPC patients and emphasize prostate cancer patients, especially those with low AR tumors. The medical needs of patients are still unmet. As we are committed to advancing the science and treatment of prostate cancer, these discoveries will help us in the development of new methods and combination treatment options to improve the prognosis of these patients. “

Zytiga (abiraterone acetate) is an oral drug that is converted to abiraterone in the body, which is an androgen biosynthesis inhibitor that blocks CYP17-mediated androgens in testis, adrenal glands and prostate tumor tissues Produced, and androgens can stimulate the growth of prostate cancer cells.

Zytiga was approved by the US FDA in April 2011 and the European Commission (EC) in September 2011, combined with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). In addition, Zytiga was approved by the EC in November 2017 and the FDA in February 2018 for the treatment of patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC). Since it was first approved in 2011, the drug has been approved in more than 100 countries around the world, and more than 500,000 patients have been treated with Zytiga worldwide.

Erleada (apatamide) is a new generation of androgen receptor (AR) inhibitors that can help block the activity of male hormones (such as testosterone hormone) and delay the progression of the disease. In the United States, Erleada was first approved by the FDA in February 2018 for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) at high risk of metastasis.

This approval makes Erleada the world’s first drug to treat nmCRPC. In September 2019, the FDA approved Erleada as a new indication for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).

(source:internet, reference only)

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