Data from the pivotal phase 3 LATITUDE clinical trial showed Abiraterone acetate ( Zytiga ) plus Prednisone, in combination with androgen deprivation therapy ( ADT ), demonstrated a significant improvement in overall survival ( OS ) and significantly prolonged radiographic progression-free survival ( rPFS ) in patients with high-risk metastatic hormone-naïve prostate cancer ( mHNPC ) compared to placebo plus ADT.
Study findings have indicated Abiraterone acetate plus Prednisone, in combination with ADT, reduced the risk of death by 38% compared to placebo plus ADT ( hazard ratio [ HR ]=0.62; 95% CI [ 0.51 to 0.76 ], P less than 0.0001 ).
Median overall survival ( OS ) for the Abiraterone acetate plus Prednisone in combination with ADT arm was not reached, while the median overall survival for the placebo plus ADT arm was 34.7 months.
Additional study results found Abiraterone acetate plus Prednisone, in combination with ADT, decreased the risk of progression or death rPFS by 53% compared to placebo plus ADT in patients with mHNPC ( HR=0.47%, 95% CI [ 0.39 to 0.55 ], P less than 0.0001 ). Median rPFS was 33.0 months in the Abiraterone acetate plus Prednisone with ADT group, compared to 14.8 months with placebo plus ADT.
Historically, androgen deprivation therapy ( ADT ) has been the standard of care for patients with metastatic prostate cancer.
ADT is often very effective at shrinking or slowing the growth of prostate cancer that has spread, but it usually becomes less effective over time.
In addition to meeting the primary endpoints of overall survival and rPFS, the Abiraterone acetate plus Prednisone with ADT arm also met all secondary endpoints, with statistically significant improvements in times to pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, prostate-specific antigen ( PSA ) progression ( P less than 0.0001 ), and symptomatic skeletal events ( p=0.0086 ).
Overall, the safety profile of ADT in combination with Abiraterone acetate plus Prednisone was consistent with prior studies in patients with metastatic castration-resistant prostate cancer ( mCRPC ).
Grade 3/4 events reported in greater than or equal to 5% of patients were hypertension ( 20%/0% versus 10%/0.2% ), hypokalemia ( 10%/0.8% vs 1%/0.2% ) and alanine aminotransferase increased ( 5%/0.3% vs 1%/0% ) in the Abiraterone acetate plus Prednisone with ADT versus placebo with ADT groups, respectively.
The phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled LATITUDE study enrolled 1,199 newly diagnosed patients with high-risk metastatic hormone-naïve prostate cancer and was conducted at 235 sites in 34 countries in Europe, Asia-Pacific, Latin America, and Canada.
A total number of 597 patients were randomized to receive ADT in combination with Abiraterone acetate plus Prednisone ( n=597 ), while 602 patients were randomized to receive ADT and placebo ( n=602 ).
Patients included had high-risk mHNPC documented by positive bone scan or metastatic lesions at the time of diagnosis on computed tomography ( CT ) or magnetic resonance imaging ( MRI ).
Additionally, patients had to have at least two of the three following high-risk factors associated with poor prognosis: Gleason score greater than or equal to 8, gretaer than or equal to 3 bone lesions and presence of measurable visceral metastases.
Abiraterone blocks CYP17-mediated androgen production, which fuels prostate cancer growth, at three sources: in the testes, adrenals and the prostate tumor tissue. It has proven efficacy in patients with mCRPC who have progressed on androgen deprivation therapy.
Not all prostate cancer is the same. It ranges from cancer confined to the prostate gland to cancer that has spread outside of the prostate to the lymph nodes, bones, or other parts of the body.
The extent or spread of prostate cancer determines the stage.
Patients with high-risk metastatic hormone-naïve prostate cancer have at least two of the following factors: Gleason score of eight or above, presence of three or more lesions on a bone scan, or presence of measurable visceral metastasis on CT or MRI, excluding lymph node disease.
Hormone-naïve prostate cancer ( HNPC ) refers to a stage of the disease when the patients have not yet received hormone therapy or androgen deprivation therapy.
HNPC is further categorized into biochemical recurrence ( in which patients have a rising prostate-specific antigen [ PSA ] after treatment, but the tumor is still localized ) and metastatic prostate cancer ( in which the cancer has spread or metastasized to other parts of the body ).
Patients with newly diagnosed mHNPC, particularly with high-risk characteristics, have a poor prognosis.
ADT plus Docetaxel has shown improved outcomes in mHNPC, but many patients are not candidates for Docetaxel and may benefit from alternative therapy.
Also, while the majority of patients initially start on ADT, it usually becomes less effective over time. ( Xagena )
Source: Janssen, 2017