Bright White Light May Offset Negative Effects of ADT in Older Men With Prostate Cancer

For older patients with prostate cancer, bright white light could potentially mitigate the negative effects of androgen deprivation therapy (ADT) with abiraterone acetate (Zytiga) or enzalutamide (Xtandi), on elements of obese frailty, according to Tanya Dorff, MD.

In a randomized clinical trial (NCT03661437), older patients who were aged 60 years or older with prostate cancer who were receiving ADT with abiraterone or enzalutamide were randomized 1:1 to receive bright white light or dim white light. Results indicated that those in the bright white light arm had a significant improvement in muscle strength. Moreover, those who received bright white light did not have a decline in energy levels and they did not experience any gain in waist circumference.

“This is something that should be studied further. It is a very non-toxic intervention [in which] the patient wears a visor that is giving them bright white light for 30 minutes per day,” Dorff said. “They wear [the visor] in the morning, and it just taps into that rhythm of the day, and the importance of sleep-wake and light in setting our bodies for the right kind of cycle. This probably is working primarily through better sleep, and maybe better energy. It was a very interesting study, even though it was small.”

In an interview with OncLive^®, Dorff, a medical oncologist and an associate clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, discussed encouraging data from a study evaluating bright white light in older patients with prostate cancer and updates from the phase ARAMIS trial (NCT02200614).

OncLive^®: What were the key findings of the recent study that examined the effects of bright white light therapy on obese frailty in older men with prostate cancer on hormonal therapy?

Dorff: William Dale, MD, PhD, from our Department of Supportive Medicine [at City of Hope], who specializes in geriatric oncology, designed this interesting study based on strong preclinical data. [The research] compared bright white light with regular light to see whether it would reduce frailty during ADT in our [patients with] prostate cancer. The study was designed for our [older patients], who were at least 60 years of age, and those [who are heavier], with a higher waist circumference, to have the maximum impact, because hormone therapy has the greatest potential to cause harm in this population.

Although the study had to be closed early due to [the COVID-19 pandemic], 18 patients were randomized. Even in that small number of patients, it was impressive [to see] a reduction in the amount of loss of strength, as measured by grip strength, and there was a better maintenance of energy. We know androgen deprivation [therapy] induces fatigue in many of our patients, and that effect was mitigated by this bright white light. [Additionally,] waist circumference did not increase as much, and we know that is something that can change due to metabolic changes with ADT.

We are just looking at these data now, so we are going to have to go back and make plans for next steps. A larger study in a similar population would be a good place to start, and maybe including more patients who are on the more intensive agents, like the androgen receptor–targeted agents.

Switching over to the ARAMIS trial, could you provide some background on this study and how it has impacted the prostate cancer treatment paradigm?

The ARAMIS trial [examined] patients with nonmetastatic castration-resistant prostate cancer [nmCRPC]. [These patients have] rising prostate-specific antigen [PSA], we treat them with hormone therapy, it works for a while, and then their PSA rises again. [However,] when we scan [these patients], we do not find any sites of metastases. [In the] ARAMIS trial [we] used darolutamide [Nubeqa] compared with placebo, and castration therapy was continued. It was a very large trial, and it did include patients only with a PSA doubling time of less than, or equal to, 10 months. This trial was very similar to trials with enzalutamide and apalutamide [Erleada] that all came out one after the other.

The bottom line is that we now have an agent that we know. With darolutamide, when we use it for [patients with] nmCRPC, we delay the time until metastatic disease, which should mean that we delay the time until they feel their cancer or have deterioration in quality of life [QoL]. That is, in fact, what we saw with the QoL analyses. By managing the cancer effectively, patients do not end up having many symptoms that are mostly because of the cancer, and fortunately, less because of the treatment. That is the other important aspect: Not only is the drug effective, but it is very well tolerated.

Could you expand upon what makes darolutamide a unique agent in this space? Are any other research efforts examining this agent underway?

One of the drawbacks of the androgen receptor–targeted agents like enzalutamide, which has been around the longest, is that we have seen some frailty symptoms like falls or loss of muscle strength. We have also seen some cognitive changes, or even more emotional changes, like anxiety. These can be difficult for patients, so one of the reasons we were interested in darolutamide is the design [of the agent]. The structure of the molecule is such that it should not cross the blood–brain barrier, and this should theoretically reduce the amount of some of these cognitive or central nervous system [CNS]–type adverse effects.

Although it has not yet been compared head-to-head against the other drugs, if you just look within each trial—apalutamide vs placebo, darolutamide vs placebo—and you look at the differences within each trial, you see a greater amount of falls, and CNS toxicity [with] enzalutamide vs placebo, and to some extent, apalutamide vs placebo. The numbers in the darolutamide trial, [however], look very similar. We have taken this to indicate that, in fact, the biology is translating into what we are seeing in our patients. Clinically, I have used all the agents, and generally they are all very well tolerated. Darolutamide has a very nice, clean toxicity profile.

The survival advantage and metastasis-free survival advantage that was seen in ARAMIS, as well as other trials in nmCRPC, to me, fit with the overall trend that we saw 5 or 6 years ago, where bringing our therapies from castration-resistant metastatic disease up front to castration-sensitive [disease] made a huge impact on survival. It just speaks to the fact that controlling the cancer better, attacking it more aggressively from the start, or earlier in the disease, pays big dividends over the long haul.

Reference

Bergerot CD, Razavi M, Celis A, et al. The effects of bright white light therapy on obese frailty in older men with prostate cancer on hormonal therapy: a pilot randomized control trial. J Clin Oncol. 2021;39(suppl 6):75. doi:10.1200/JCO.2021.39.6_suppl.75