Apalutamide Does Not Impact Patient-Reported Side Effect Burden, HRQOL in mCSPC

Prostate cancer

The addition of apalutamide (Erleada) to androgen deprivation therapy (ADT) does not lead to a significant patient-reported side effect burden nor a reduction in health-related quality of life (HRQOL) in patients with metastatic castration-sensitive prostate cancer (mCSPC), according to the final analysis of the phase 3 TITAN trial (NCT02489318). The data were presented during the 47th Annual Oncology Nursing Society (ONS) Congress.¹

Results showed that the favorable baseline FACT-P scores did not worsen to a clinically relevant degree over time in the apalutamide or placebo groups. Adding apalutamide 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 33 treatment cycles.

There were no significant differences between groups in 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 during the meeting. “These patient-reported findings further support the robust safety and efficacy of apalutamide added to ADT demonstrated in the TITAN study.”

In the double-blind TITAN trial, investigators enrolled 1052 patients with mCSPC who were receiving treatment with ADT to receive either apalutamide orally at 240 mg daily (n = 525) or placebo (n.= 527). Investigators were also blinded to prostate-specific antigen responses through cycle 4.

Primary findings from the study, which were at a median follow-up of 22.7 months, showed that apalutamide led to a significant improvement in radiographic progression-free survival and overall survival (OS) vs placebo, while also preserving HRQOL.^2,3

Patients on the placebo arm were permitted to cross over to apalutamide following unblinding.

At a median follow-up of 44.0 months, the OS benefit was confirmed in the final analysis with a 35% reduction in the risk of death with apalutamide despite cross over.⁴

Apalutamide gained FDA approval in September 2019 for the treatment of patients with metastatic castration-sensitive prostate cancer, based on the primary TITAN results.⁵

In the analysis presented at the ONS Congress, which was also presented during the 2021 ASCO Annual Meeting⁶, investigators sought to evaluate the HRQOL and adverse effect (AE) burden at the final analysis of TITAN to better understand the impact of adding the androgen receptor inhibitor to ADT.

At the final analysis, the median treatment duration was 39.3 months with apalutamide and 20.2 months for placebo.

The mean patient-reported outcome (PRO) scores were reported over time by patients in each treatment group. PRO tools included:

1. 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.
2. 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.
3. FACT-P, which assesses HRQOL in men with prostate cancer. This was completed at baseline, at cycles 2 to 7, and then 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 groups by fitting proportional hazards regression models.

Baseline characteristics were well balanced between the 2 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 similar between the 2 groups.

In terms of pain and fatigue, patients were relatively asymptomatic with good baseline HRQOL. On the BPI-SF pain score, patients reported having no pain (38%), mild pain (38%), moderate (18.5%), or severe (2%). For BFI-fatigue, patients reported no fatigue (33%), mild (42%), moderate (18.5%), or severe (2.5%).

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. Furthermore, more than 75% of patients across the trial had mild to zero fatigue.

Additional data showed that favorable baseline BPI scores were stable over time in both arms, and this included worst pain intensity scores. In terms of side effects bother, more than 86% of patients on apalutamide and 85% on placebo were either “not at all” or “a little bit” bothered by side effects.

In relation to energy, more than 78% and 71% of patients on apalutamide and placebo, respectively, 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.

References

1. 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.
2. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide formetastatic, castration-sensitive prostate cancer. N Eng J Med. 2019;381(1):13-24. doi:10.1056/NEJMoa1903307.
3. 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 randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019;20(11):1518-1530. doi:10.1016/S1470-2045(19)30620-5.
4. 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.
5. U.S. 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 2, 2022. https://prn.to/2kRwT6m
6. 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