The addition of apalutamide to androgen deprivation therapy was not found to significantly reduce health-related quality of life or increase patient-reported adverse effect burden.
The addition of apalutamide (Erleada) to androgen deprivation therapy (ADT) was not found to significantly reduce health-related quality of life (HRQOL) or increase patient-reported adverse effect (AE) burden, according to findings from the final analysis of the phase 3 TITAN trial (NCT02489318) presented during the 47th Annual Oncology Nursing Society (ONS) Congress.one
In the apalutamide or placebo arms, favorable baseline FACT-P scores did not worsen to a clinically relevant degree over time. Moreover, the addition of apalutamide to ADT did not worsen any individual FACT-P HRQOL measures—FACT-P Total Score, Physical Wellbeing Score, Emotional Wellbeing Score, Functional Wellbeing Score, Social/Family Wellbeing Score, Prostate Cancer Subscale Score, Trial Outcome Index, and FACT-G Score—over the course of 33 treatment cycles.
Additionally, no significant differences were observed between the arms with regard to median time to deterioration in any Brief Pain Inventory (BPI) or Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores, including BPI Worst Pain (apalutamide, 19.32 months). [range, 11.01-27.70] vs placebo, 11.99 months [range, 8.28-18.46]; HR, 0.89; 95% CI, 0.75-1.05; P = .1665), BPI Pain Interference (not estimable [NE; range, 40.54-NE] vs NE [range, 30.39-NE], respectively; HR, 0.91; 95% CI, 0.75-1.10; P = .3204), FACT-P Total (9.00 months [range, 5.55-11.14] vs 9.23 months [range, 7.39-12.91], respectively; HR, 0.97; 95% CI, 0.82-1.16; P = .7643), and FACT-G (11.10 months [range, 9.17-14.75] vs 11.04 months [range, 7.72-13.70]; HR, 0.93; 95% CI, 0.78-1.11; P = .4318).
“Key takeaways from this in-depth analysis of patient-reported quality of life in patients with mCSPC in the TITAN final analysis include confirmation that the addition of apalutamide to ADT did not worsen HRQOL or side effect burden,” lead study author Jennifer Lloyd MSN , FNP-C, OCN, an oncology nurse practitioner at Huntsman Cancer Institute, said in a virtual poster presentation. “These patient-reported findings further support the robust safety and efficacy of apalutamide added to ADT demonstrated in the TITAN study.”
TITAN enrolled a total of 1052 patients with mCSPC who were receiving treatment with ADT; they were randomized to receive either oral apalutamide at a daily dose of 240 mg (n = 525) or placebo (n = 527). Investigators were blinded to prostate-specific antigen responses through cycle 4.
Primary data from the study, which had a median follow-up of 22.7 months, revealed that apalutamide significantly improved radiographic progression-free survival and overall survival (OS) compared with placebo; the agent was also found to preserve HRQOL.23
Notably, patients on the placebo arm were allowed to cross over to apalutamide following unblinding.
At the time of the final analysis, which had a median follow-up of 44.0 months, the OS benefit was confirmed with a 35% reduction in the risk of death with apalutamide despite crossover.4
In September 2019, the FDA approved apalutamide for the treatment of patients with metastatic castration-sensitive prostate cancer, based on the primary results from TITAN.5
In the analysis presented at the ONS Congress, which was also presented during the 2021 ASCO Annual Meeting,6 investigators set out to assess the HRQOL and AE burden to better understand the impact of adding the androgen receptor inhibitor to ADT.
At the final analysis, the median treatment duration with apalutamide was 39.3 months and 20.2 months with placebo.
The mean patient-reported outcome (PRO) scores were reported over time by patients in each treatment group. PRO tools included:
- BPI-Short Form (BPI-SF), which evaluates pain severity and its impact on daily functioning, and was completed for 7 days consecutively (days -6 to 1 of each 28-day cycle) through the end of treatment.
- Brief Fatigue Inventory (BFI), which assesses the severity and impact of cancer-related fatigue and was completed for 7 consecutive days (days -6 to 1 of each 28-day cycle) through the end of treatment.
- FACT-P, which assesses HRQOL in men with prostate cancer. This was completed at baseline, at cycles 2 to 7, and then every other cycle through end of treatment.
Additionally, the time to deterioration of PROs was calculated via Kaplan-Meier methods and was compared between arms by fitting proportional hazards regression models.
Baseline characteristics were noted to be well balanced between the arms. The median age was 68.5 years (range, 43-94), and 36% of patients had an ECOG performance status of 1; 67.5% of patients had a Gleason score of 8 or higher and 63% of patients had high-volume disease.
Of the eligible patients per cycle, more than 62% completed the BPI form through cycle 32, and more than 50% completed FACT-P through cycle 31. Compliance was also comparable between the 2 arms.
In terms of pain and fatigue, patients were relatively asymptomatic with good baseline HRQOL. On the BPI-SF pain score, 38% of patients reported having no pain, 38% reported having mild pain, 18.5% had moderate pain, and 2% reported having severe pain. For BFI-fatigue, 33% of patients reported no fatigue, 42% had mild fatigue, 18.5% had moderate fatigue, and 2.5% had severe fatigue.
The median FACT-P total scores were 113.0 (interquartile range [IQR]98-128) with apalutamide and 113.3 (IQR, 99-127) with placebo on a scale that ranged from 0 to 156. Additionally, across the trial, more than 75% of patients had mild or no fatigue.
Additional findings indicated that favorable baseline BPI scores were stable over time in both arms, and this included worst pain intensity scores. In terms of toxicity bother, more than 86% of patients on apalutamide and 85% on placebo reported either “not at all” or “a little bit” bothered by AEs.
In relation to energy, more than 78% of those who received apalutamide and 71% of those given placebo had stable or improved energy levels that were relative to baseline levels.
“These findings provide valuable evidence-based insights aiding clinical decision-making for nurses and physicians treating patients with mCSPC,” Lloyd concluded.
- Lloyd J, Bevans KB, Dibaj S, et al. What can patients with prostate cancer expect from treatment with apalutamide? health-related quality of life in patients with metastatic castration-sensitive prostate cancer in the phase 3 TITAN study. Presented at: 47th Annual Oncology Nursing Society Congress; April 27-May 1, 2022; Anaheim, CA. Abstract P391.
- Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Eng J Med. 2019;381(1):13-24. doi:10.1056/NEJMoa1903307
- Agarwal N, McQuarrie K, Bjartell A, et al. Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomized, placebo-controlled, phase 3 study. Lancet Oncol. 2019;20(11):1518-1530. doi:10.1016/S1470-2045(19)30620-5
- Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-2303. doi:10.1200/JCO.20.03488
- US FDA approves supplemental new drug application (sNDA) for Erleada (apalutamide) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). News release. Janssen. September 17, 2019. Accessed May 3, 2022. https://prn.to/2kRwT6m
- Agarwal N, Chowdhury S, Bjartell A, et al. Health-related quality of life (HRQoL) and patient-reported outcomes at final analysis of the TITAN study of apalutamide (APA) versus placebo (PBO) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) receiving androgen deprivation therapy (ADT). J Clin Oncol. 2021;39(20):5068-5068. doi:10.1200/JCO.2021.39.15_suppl.5068