In an analysis of the phase III TITAN trial reported in The Lancet Oncology, Neeraj Agarwal, MD, and colleagues found that that treatment with apalatuamide was associated with preserved health-related quality of life, including pain and fatigue outcomes, in patients with metastatic castration-sensitive prostate cancer receiving androgen-deprivation therapy.
Neeraj Agarwal, MD
The TITAN trial showed that the addition of apalutamide vs placebo to androgen-deprivation therapy significantly improved overall survival and radiographic progression-free survival. In the double-blind trial, 1,052 patients receiving androgen-deprivation therapy were randomly assigned to apalutamide at 240 mg once daily (n = 525) or placebo (n = 527). Treatment in 28-day cycles continued until disease progression, withdrawal of consent, or unacceptable treatment-related toxicity.
Patient-reported outcomes were prespecified exploratory endpoints and were assessed by the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5 dimensions 5 levels questionnaire (EQ-5D-5L). The BPI and BFI were completed for 7 consecutive days (days −6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1 to 7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Data cutoff for the health-related quality-of-life analysis was in November 2018.
Key Findings
Patients were generally asymptomatic at baseline. On the BPI-SF pain severity scale of 0 to 10, median pain scores (indicating worst pain in the past 24 hours) were 1.14 in the apalutamide group vs 1.00 in the placebo group. On the BFI, median worst fatigue scores were 1.29 vs 1.43. Patient-reported scores of pain intensity and interference and fatigue intensity and interference did not differ between groups during the duration of treatment.
Median time to worst pain intensity progression was 19.09 months in the apalutamide group vs 11.99 months in the placebo group (hazard ratio [HR] = 0.89, P = .20). Median time to pain interference progression was not reached in either group; 25th percentiles for time to pain interference progression were 9.17 months vs 6.24 months (HR = 0.90, P = .29).
Median time to worst fatigue intensity was not reached in either group; 25th percentiles were 9.23 months vs 11.04 months (HR = 1.09, P = .44). Median time to fatigue interference progression was not reached in either group; 25th percentiles were 10.15 months vs 10.51 months (HR = 1.01, P = .93).
FACT-P total scores and EQ-5D-5L scores indicated preservation of health-related quality of life over time in both groups. Median time to deterioration according to FACT-P total score was 8.87 months vs 9.23 months (HR = 1.02, P = .85). The EQ-5D-5L health utility index declined over time and EQ-5D-5L visual analog scale scores were maintained over time in both groups.
The investigators concluded, “Apalutamide with [androgen-deprivation therapy] is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with [androgen-deprivation therapy] alone while maintaining health-related quality of life despite additive androgen blockade.”
Dr. Agarwal, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Janssen Research & Development. For full disclosures of the study authors, visit thelancet.com.
