The results from the final analysis of the phase 3 TITAN study, which has demonstrated the continued statistically significant benefit of Apalutamide ( Erleada ) plus androgen deprivation therapy ( ADT ) in overall survival ( OS ) in patients with metastatic hormone-sensitive prostate cancer ( mHSPC ) when compared to placebo plus ADT, were presented.
Apalutamide is an orally administered, selective androgen receptor ( AR ) inhibitor.
With nearly four years of median follow-up, data from the final analysis of the phase 3 TITAN study have confirmed that Apalutamide plus ADT provided statistically significant improvement in overall survival with a 35% reduction in risk of death compared to ADT alone ( hazard ratio, HR=0.65; p less than 0.0001 ).
This result was almost similar to the overall survival results in the primary analysis of TITAN despite the subsequent crossover rate of almost 40% of the placebo-controlled group to the Apalutamide arm.
The improvement in overall survival increased to a 48% reduction in risk of death after adjusting for patients who crossed over ( HR=0.52; p less than 0.0001 ).
There was consistent benefit across other endpoints, including improved second progression-free survival ( PFS2 ) ( HR=0.62; p less than 0.0001 ) and delayed time to castration resistance ( HR=0.34; p less than 0.0001 ).
In addition, health-related quality of life ( HRQoL ), per total Functional Assessment of Cancer Therapy–Prostate ( FACT-P ), continued to be maintained in both groups.
Safety of Apalutamide was consistent with previously reported studies. Observed adverse events have included skin rash, fracture, and falls.
Initial results from the TITAN study presented at the 2019 American Society of Clinical Oncology Annual Meeting ( ASCO ) and simultaneously published in The New England Journal of Medicine ( NEJM ) showed the addition of Apalutamide to ADT compared to placebo plus ADT significantly improved the dual primary endpoints of overall survival and radiographic progression-free survival ( rPFS ) in patients with metastatic hormone-sensitive prostate cancer.
To date, published results on Apalutamide include data from more than 2,000 patients across phase 3 clinical studies.
Apalutamide has shown a statistically significant improvement in overall survival with a consistent safety profile in both approved indications of mHSPC ( TITAN ) and non-metastatic castration-resistant prostate cancer or nmCRPC ( SPARTAN ).
TITAN is a phase 3, randomised, placebo-controlled, double-blind study in patients with metastatic hormone-sensitive prostate cancer, also known as metastatic castration-sensitive prostate cancer.
The study has included 1,052 patients in 23 countries across 260 sites in North America, Latin America, South America, Europe, and Asia Pacific. Patients with mHSPC were randomised 1:1 and received either Apalutamide ( 240 mg ) plus ADT ( n=525 ), or placebo plus ADT ( n=527 ).
The recruitment period for the study spanned from December 2015 to July 2017.
The study has included patients with mHSPC with both low- and high-volume disease, those who were newly diagnosed, and those who had received prior definitive local therapy or prior treatment with up to six cycles of Docetaxel for mHSPC.
Dual primary endpoints of the study were overall survival and radiographic progression-free survival. Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use, and time to skeletal-related events.
Exploratory endpoints has included time to prostate specific antigen ( PSA ) progression, PFS2 and time to symptomatic progression. ( Xagena )
Source: American Society of Clinical Oncology’s Genitourinary ( ASCO GU ) Cancers Symposium, 2021