BC Cancer and Vancouver Prostate Centre, Vancouver, BC, Canada.
Guy's and St Thomas' Hospitals, London, United Kingdom.
J Clin Oncol. 2021 Jul 10;39(20):2294-2303. doi: 10.1200/JCO.20.03488. Epub 2021 Apr 29.
The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover.
Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed.
With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance ( < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports.
The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.
III 期、随机、安慰剂对照的 TITAN 研究的首次中期分析显示，阿帕鲁胺可显著改善正在接受持续雄激素剥夺治疗（ADT）的转移性去势敏感前列腺癌（mCSPC）患者的总生存期（OS）和影像学无进展生存期（rPFS）。在此，我们报告在揭盲和安慰剂交叉至阿帕鲁胺后最终的疗效和安全性结果。
mCSPC（N=1052）患者以 1:1 的比例随机分配接受阿帕鲁胺（240 mg QD）或安慰剂加 ADT。2019 年 1 月揭盲后，允许安慰剂治疗的患者接受阿帕鲁胺治疗。使用 Kaplan-Meier 方法和 Cox 比例风险模型更新疗效终点，无需正式的重新测试和多重调整。评估基线时的癌症治疗功能评估-前列腺总评分的变化。
中位随访 44.0 个月，发生了 405 例 OS 事件，208 例安慰剂治疗患者（39.5%）交叉至阿帕鲁胺。中位治疗持续时间为 39.3 个月（阿帕鲁胺）、20.2 个月（安慰剂）和 15.4 个月（交叉）。与安慰剂相比，阿帕鲁胺加 ADT 显著降低 35%的死亡风险（中位 OS 未达到 52.2 个月；风险比，0.65；95%CI，0.53 至 0.79；<.0001），交叉调整后降低 48%（风险比，0.52；95%CI，0.42 至 0.64；<.0001）。阿帕鲁胺加 ADT 还延迟了第二次无进展生存期和去势抵抗（均<.0001）。根据癌症治疗功能评估-前列腺总评分，两组的健康相关生活质量均在研究期间得以维持。安全性与之前的报告一致。
TITAN 的最终分析证实，尽管存在交叉，阿帕鲁胺加 ADT 仍可改善 OS、延迟去势抵抗、维持健康相关生活质量，并在广泛的 mCSPC 患者人群中具有一致的安全性。
