Genitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
Genitourinary Malignancies, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
J Immunother Cancer. 2021 Mar;9(3). doi: 10.1136/jitc-2020-001556.
The standard treatment for non-metastatic castration sensitive prostate cancer (nmCSPC) is androgen deprivation therapy (ADT) or surveillance. This study evaluated the potential synergy of immunotherapy and enzalutamide (without ADT) in nmCSPC. In addition, the immunologic impact of enzalutamide was also evaluated in men with normal testosterone.
Patients with rising prostate-specific antigen (PSA) after definitive therapy, normal testosterone and no radiographic metastasis were randomized to enzalutamide for 3 months with/without PROSTVAC for 6 months. Thereafter, patients could be retreated with another 3 month course of enzalutamide when PSA returned to baseline. Immune profiles were evaluated in these patients.
Thirty-eight patients were randomized with a median PSA=4.38 ng/dL and PSA doubling time=4.1 months. No difference was observed between the two groups for PSA growth kinetics, but PSA responses to enzalutamide were noteworthy regardless of PROSTVAC. The median PSA decline after short-course enzalutamide without ADT/testosterone lowering therapy was 99% in both courses. The median time to PSA recovery to baseline after each 84-day course of enzalutamide was also noteworthy because of the duration of response after enzalutamide was discontinued. After the first and second 3 month cycle of enzalutamide, PSA recovery to baseline took a median 224 (range 84-1246) and 189 days (78-400), respectively. The most common adverse events related to the enzalutamide were grade 1 fatigue (71%) and grade 1 breast pain/nipple tenderness (81%). The only grade 3 toxicity was aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation in two patients. Enzalutamide was independently associated with immune changes, increasing natural killer cells, naïve-T cells, and decreasing myeloid-derived suppressor cells.
Three months of enzalutamide without ADT induced substantial PSA control beyond the treatment period and was repeatable, perhaps representing an alternative to intermittent ADT in nmCSPC. In addition, enzalutamide was associated with immune changes that could be relevant as future immune combinations are developed. TRAIL REGISTRATION NUMBER: clinicaltrials.gov (NCT01875250).
非转移性去势敏感型前列腺癌（nmCSPC）的标准治疗方法是雄激素剥夺疗法（ADT）或监测。本研究评估了免疫疗法与恩扎卢胺（无 ADT）联合治疗 nmCSPC 的潜在协同作用。此外，还评估了恩扎卢胺对睾酮正常的男性的免疫影响。
接受根治性治疗后前列腺特异性抗原（PSA）升高、睾酮正常且无影像学转移的患者被随机分配至恩扎卢胺治疗 3 个月，加或不加 PROSTVAC 治疗 6 个月。此后，当 PSA 恢复至基线时，患者可以再接受另外 3 个月的恩扎卢胺治疗。对这些患者进行免疫谱评估。
38 例患者被随机分配，中位 PSA=4.38ng/dL，PSA 倍增时间=4.1 个月。两组患者的 PSA 增长动力学无差异，但无论是否使用 PROSTVAC，恩扎卢胺的 PSA 反应均值得注意。在不进行 ADT/降低睾酮治疗的情况下，短期恩扎卢胺治疗后 PSA 下降中位数为 99%，两疗程均如此。由于恩扎卢胺停药后反应持续时间，每次 84 天疗程后 PSA 恢复至基线的中位时间也值得注意。在第一次和第二次 3 个月的恩扎卢胺周期后，PSA 恢复至基线的中位时间分别为 224（范围 84-1246）和 189 天（78-400）。与恩扎卢胺相关的最常见不良事件为 1 级疲劳（71%）和 1 级乳房疼痛/乳头触痛（81%）。仅 2 例患者出现 3 级毒性，即天冬氨酸氨基转移酶（AST）/丙氨酸氨基转移酶（ALT）升高。恩扎卢胺与免疫变化独立相关，增加自然杀伤细胞、幼稚 T 细胞，减少髓系来源抑制细胞。
无 ADT 的 3 个月恩扎卢胺治疗可在治疗期间后显著控制 PSA，并可重复，这可能是 nmCSPC 间歇性 ADT 的替代方案。此外，恩扎卢胺与免疫变化相关，这可能与未来的免疫联合治疗有关。
clinicaltrials.gov（NCT01875250）。
