在携带生殖系 BRCA 突变的局部晚期或转移性乳腺癌的日本患者中，talazoparib 的疗效和安全性：I 期剂量扩展研究的结果。
Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study.
机构信息
Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka-shi, Osaka, 540-0006, Japan.
出版信息
Breast Cancer. 2022 Nov;29(6):1088-1098. doi: 10.1007/s12282-022-01390-w. Epub 2022 Jul 30.
BACKGROUND
Talazoparib, a poly(ADP-ribose) polymerase enzyme inhibitor, is approved for the treatment of patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative advanced breast cancer. This two-part study, a recently published dose-escalation part followed by the dose-expansion part reported here, evaluated the efficacy and safety of talazoparib in Japanese patients with gBRCA1/2-mutated advanced breast cancer.
METHODS
In this open-label, multicenter phase 1 study (NCT03343054), the primary endpoint of the dose-expansion part was confirmed objective response rate (ORR), determined by investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Patients received the recommended phase 2 dose (1 mg/day; 0.75 mg/day moderate renal impairment).
RESULTS
Nineteen Japanese patients with gBRCA1/2-mutated locally advanced or metastatic breast cancer were enrolled. Confirmed ORR was 57.9% (11/19; 90% confidence interval [CI] 36.8-77.0). Stable disease was observed in 36.8% (7/19) of patients. Per investigator assessment, median PFS was 7.2 months (95% CI 4.1-not estimable) and 12-month OS rate was 84.7% (90% CI 57.5-95.1). Median OS was not reached; 17/19 patients were alive and censored at 12 months. All patients experienced treatment-related adverse events (AEs); the majority were hematologic. The most common treatment-related AE was anemia (68.4%; [13/19]). Grade 3/4 treatment-related AEs were observed in 52.6% (10/19) of patients. During the safety period, there were no grade 5 treatment-emergent AEs, treatment-related serious AEs, or deaths.
CONCLUSIONS
In Japanese patients with gBRCA mutations and locally advanced or metastatic breast cancer, talazoparib monotherapy was generally well tolerated and resulted in clinically meaningful ORRs.
GOV IDENTIFIER
NCT03343054.
背景
Talazoparib 是一种聚（ADP-核糖）聚合酶酶抑制剂，已获批用于治疗携带生殖系 BRCA1/2（gBRCA1/2）突变的 HER2 阴性晚期乳腺癌患者。这项两部分的研究，一部分是最近发表的剂量递增部分，另一部分是此处报道的剂量扩展部分，评估了 talazoparib 在日本 gBRCA1/2 突变的晚期乳腺癌患者中的疗效和安全性。
方法
在这项开放标签、多中心的 1 期研究（NCT03343054）中，剂量扩展部分的主要终点是由研究者评估（RECIST 1.1）确认的客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）、安全性和药代动力学。患者接受推荐的 2 期剂量（1mg/天；中度肾功能损害时为 0.75mg/天）。
结果
19 名携带 gBRCA1/2 突变的局部晚期或转移性乳腺癌患者入组。确认的 ORR 为 57.9%（11/19；90%置信区间 [CI] 36.8-77.0）。36.8%（7/19）的患者疾病稳定。研究者评估的中位 PFS 为 7.2 个月（95%CI 4.1-不可估计），12 个月 OS 率为 84.7%（90%CI 57.5-95.1）。中位 OS 未达到；17/19 名患者存活且在 12 个月时被删失。所有患者均发生治疗相关不良事件（AE）；大多数为血液学相关。最常见的治疗相关 AE 是贫血（68.4%[13/19]）。52.6%（10/19）的患者发生 3/4 级治疗相关 AE。在安全性期间，无 5 级治疗相关 AE、治疗相关严重 AE 或死亡。
结论
在日本携带 gBRCA 突变的局部晚期或转移性乳腺癌患者中，talazoparib 单药治疗总体耐受性良好，并且具有有临床意义的 ORR。
政府标识符
NCT03343054。
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