Bone Metastasis Count May Guide Erleada Treatment in Prostate Cancer

The addition of Erleada (apalutamide) to androgen-deprivation therapy (ADT) may provide less benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC) and fewer bone metastases, according to study findings published in American Cancer Society.

In addition, counting baseline bone metastases may aid identification of optimal candidates for Erleada treatment of mCSPC.

After a median follow-up of 44 months, an analysis of the phase 3, randomized, double-blind TITAN study showed that Erleada offered less benefit for second progression-free survival (PFS2) — the time from randomization to either disease progression during the first treatment after the study or death from any cause — and overall survival (OS) in patients with fewer bone metastases. Researchers found differences in how patients responded to Erleada based on the number of bone metastases, with no observed benefit for radiographic progression-free survival, PFS2 or OS in those with two or fewer bone metastases. In this group, the risk of radiographic progression was reduced by 35%, while the risk of second progression increased by 18% and the risk of death increased by 5%. The presence of visceral metastases was not associated with Erleada benefit.

“Our findings suggested a lesser benefit from the addition of [Erleada] to ADT in patients with mCSPC whose bone metastasis counts were relatively low at baseline,” wrote leading study author Dr. Wataru Fukuokaya and collogues. “We did not observe an association between visceral metastasis and the benefit of adding [Erleada]. Encouraging a bone metastasis count at baseline may help guide treatment optimization in this population.”

Fukuokaya is affiliated with the Department of Clinical Biostatistics at the Institute of Science Tokyo in Tokyo, Japan, and the Department of Urology at The Jikei University School of Medicine, also in Tokyo.

Regarding safety of the TITAN trial, patients who received Erleada plus ADT stayed on treatment a median of 19.1 months longer than those who received placebo plus ADT (39.3 months versus 20.2 months). In the crossover group, the median treatment duration with Erleada was 15.4 months. Overall rates of treatment-emergent side effects were similar across the groups. Rates of severe or serious side effects and common events such as falls, fractures and fatigue were also comparable. Skin rash, which was more common in Erleada-treated patients, typically developed within the first six months and then plateaued. The most frequent Erleada-related side effects were rash and fatigue. No treatment-related deaths were reported. Three patients in the crossover group experienced COVID-19-related side effects that resolved without leading to treatment discontinuation or death.

Among 1052 patients included in the TITAN study, 525 were assigned to the Erleada group and 527 were assigned to the placebo group. A total of 208 patients in the placebo group switched to Erleada because of crossover. Patients were randomly assigned to receive either Erleada (240 milligrams once a day in 28 treatment cycles)) plus ADT or a placebo (matching dose) plus ADT. After the study was unblinded in January 2019, those initially given a placebo were allowed to start Erleada.

Exclusion criteria for the study included patients with pathological findings consistent with small cell, ductal or neuroendocrine carcinoma of the prostate, known brain metastases, or lymph nodes as the only site of metastasis. Additionally, patients with visceral metastases, such as those in the liver or lungs, as the only sites of metastasis were excluded. Those with a history of other malignancies within the last five years, except for squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer, were also excluded. Patients who had prior treatment with other next-generation anti-androgens, CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer were not eligible. Finally, individuals with a history of seizures or those taking medications known to lower the seizure threshold were excluded.

References

1. “Tumor burden and heterogenous treatment effect of apalutamide in metastatic castration-sensitive prostate cancer,” by Dr. Wataru Fukuokaya, et al., American Cancer Society.
2. “Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study,” by Dr. Kim N. Chi, et al., Journal of Clinical Oncology.

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