The addition of enzalutamide to androgen deprivation therapy (ADT) led to maintained health-related quality of life and low symptom burden versus placebo and ADT in men with metastatic castration-sensitive prostate cancer.
The addition of enzalutamide (Xtandi) to androgen deprivation therapy (ADT) led to maintained health-related quality of life (HRQOL) and low symptom burden versus placebo and ADT in men with metastatic castration-sensitive prostate cancer (mCSPC), according to an analysis from the phase 3 ARCHES trial.
On December 17, 2019, the FDA approved a supplemental new drug application for enzalutamide for the treatment of patients with mCSPC, according to findings from ARCHES which showed that enzalutamide led to a 61% reduction in the risk of radiographic progression or death versus placebo (HR, 0.39; 95% CI, 0.30-0.50; P <.0001).1
In the HRQOL analysis, patient-reported outcomes (PROs) were assessed at baseline, week 13, and every 12 weeks until disease progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate 25 (QLQ-PR25), Functional Assessment of Cancer Therapy-Prostate (FACT-P), Brief Pain Inventory Short Form, and EuroQOL 5-Dimensions, 5-Levels (EQ-5D-5 L) instruments.
PRO scores reflected high HRQOL and low pain at baseline. No statistically significant differences were reported in the time to first (TTFD) and first confirmed (TTFCD) clinically meaningful deterioration in HRQOL and pain between arms for QLQ-PR25 and FACT-P scores (nominal P > 0.05).2
However, enzalutamide led to a significant delay in the TTFD in worst pain by approximately 3 months (nominal P = 0.032), pain severity (nominal P = 0.021), and EQ-5D-5 L visual analogue scale score (nominal P = 0.0070) versus placebo.
“In looking at the severity of the disease and the [likelihood] of not only developing metastasis but of eventually dying from the disease, that we are able to give patients a drug earlier, which may then reduce pain, urinary problems, bowel problems, and undisturbed QOL [is wonderful],” said Arnulf Stenzl, MD, medical director of the Department of Urology at the University of Tübingen and lead author of the HRQOL analysis. “Being able to deliver the QOL that patients deserve, at least for a time, despite the severity of the disease and the psychological impact it has on patients, is something we [always strive for].”
In an interview with OncLive, Stenzl discussed the entrance of enzalutamide into the mCSPC paradigm and detailed key findings from the initial and exploratory analyses of the ARCHES trial.
OncLive: Could you discuss the benefit enzalutamide offers to patients with mCSPC?
Stenzl: [Enzalutamide] postpones the development of metastasis, which provides an advantage for patients with regard to how they feel about their disease and how they’re going to plan for the pain and restrictions that may come with metastases.
Could you speak to the data from the ARCHES trial that served as the basis for the FDA approval of enzalutamide in this setting?
The study showed that giving enzalutamide at a very early stage could postpone [the development of] metastases and all the consequences that come with that. In parallel, studies had shown that docetaxel postpones the [development] of the disease if given at the initial phase of hormone ablation therapy. After that study, the discussion focused on whether patients with high-volume disease were the only ones who derived real benefit [from docetaxel].
Subsequently, the trial that evaluated abiraterone acetate (Zytiga) showed that giving abiraterone instead of docetaxel really does influence the course of disease. However, we don’t know whether [the benefit is] only high-risk patients, which the investigators defined by [a certain] number of metastases in the bone, the location in the bone, and the presence or absence of visceral metastasis.
Now, we have the opportunity to give patients an antiandrogen drug that is neither a chemotherapy nor influences corticosteroids levels and adrenal hormones. [Abiraterone acetate] can be given independent of meals during the day and has a very good adverse effect (AE) profile.
Could you expand on the safety profile of enzalutamide?
The safety profile is very favorable. Of course, you have to be careful with all of [the antiandrogens] in terms of fatigue. We do not see any of the brain-related AEs which we can sometimes see with enzalutamide. [Enzalutamide] is very well tolerated, according to the objective data and the patient-reported data, which showed that the QOL in these patients was unchanged. We didn’t see a decline in QOL, despite the fact that it was given at an earlier stage than we’re used to in the nonmetastatic and metastatic castration-resistant settings.
How was QOL assessed? What were some of the questions that patients were asked?
Several tools are used for QOL analyses in oncology. These tools included functional psychological outcomes and feelings of the patient. We saw a very nice picture of how these patients were responding to enzalutamide despite being a potent drug. The [drug-related AEs] evened out the [symptoms] of the disease so that men could continue their normal lives while [delaying] the development of metastases.
Could you expand on what the analysis showed?
In the paper, we showed that [patients experienced] very nice physical and emotional well-being. [In addition to] social and family wellbeing, [we also saw] other factors that we [attribute] to QOL. Not all pain-related factors did improve, but the development of pain and the time to worsening of pain were all things that were affected with enzalutamide. Other drugs would be more of a stress or a burden to these patients. For example, with intravenous chemotherapy, patients would have to go to a hospital.
It’s always really difficult to [turn] these pain-related factors [into scores] because the patient experiences pain, not only from the disease but from old age, or other comorbidities.
What questions remain with enzalutamide? Where should future research with this agent focus?
Everything is about combinations right now. We have new hints that some of the checkpoint inhibitors may [be effective] in some patients with prostate cancer. [Enzalutamide may be an optimal combination partner for] checkpoint inhibitors in the early metastatic setting.
We’ll also want to think about [what to do for patients] with severe disease [who are receiving] local therapy. At the time of treatment, is it possible to give perioperative therapy, presumably curative or locally ablative therapies like radiotherapy in combination?
Is there anything else you would like to add?
Everyone wants to know how the coronavirus disease 2019 (COVID-19) pandemic is impacting the use of enzalutamide. In clinical practice, we have not seen anything that suggests that [enzalutamide] may worsen the risk of COVID-19 infection or that COVID-19 interferes with the use of the agent.