FDA批准图卡替尼联合曲妥珠单抗与帕妥珠单抗维持治疗HER2阳性乳腺癌：中位无进展生存期24.9个月
美国食品药品监督管理局（FDA）10月7日批准图卡替尼（tucatinib，商品名Tukysa，生产商为辉瑞旗下Seagen公司）联合曲妥珠单抗与帕妥珠单抗，用于不可切除的局部晚期或转移性HER2阳性乳腺癌成人患者在诱导治疗后的维持治疗。
批准基于HER2CLIMB-05随机、双盲、安慰剂对照试验：654名患者在诱导治疗后随机接受图卡替尼每日两次口服300毫克（或安慰剂），联合曲妥珠单抗与帕妥珠单抗静脉给药或固定剂量皮下复方制剂。结果显示，图卡替尼组中位无进展生存期为24.9个月（95%置信区间21.3至尚未达到），对照组为16.3个月（95%置信区间12.6至18.7），风险比0.64（95%置信区间0.51至0.80，p<0.0001），即疾病进展或死亡风险降低36%。在无进展生存期分析时，总生存期数据尚不成熟。
FDA提示图卡替尼带有肝毒性黑框警告，另需注意腹泻、胚胎-胎儿毒性，以及不影响肾功能的血清肌酐升高等风险。HER2阳性乳腺癌是侵袭性较强的亚型，这一口服小分子加入维持方案，为患者在诱导治疗后提供了延续双靶向压制加口服药的新组合；是否适用须由肿瘤专科医生结合病情评估。
FDA Approves Tucatinib Maintenance Regimen for HER2-Positive Breast Cancer; Median Progression-Free Survival 24.9 Months
The US Food and Drug Administration on October 7 approved tucatinib (Tukysa, made by Seagen, a Pfizer subsidiary) in combination with trastuzumab and pertuzumab for the maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.
The approval is based on HER2CLIMB-05, a randomized, double-blind, placebo-controlled trial of 654 patients who, after induction therapy, received tucatinib 300 mg orally twice daily or placebo, each combined with trastuzumab and pertuzumab given intravenously or as a fixed-dose subcutaneous combination. Median progression-free survival was 24.9 months (95% CI 21.3–not reached) with tucatinib versus 16.3 months (95% CI 12.6–18.7) with placebo, a hazard ratio of 0.64 (95% CI 0.51–0.80; p<0.0001) — a 36% reduction in the risk of progression or death. Overall survival data were not mature at the time of the analysis.
Tucatinib carries a boxed warning for hepatotoxicity, along with warnings for diarrhea, embryo-fetal toxicity and increases in serum creatinine that do not reflect impaired renal function. HER2-positive disease is an aggressive breast cancer subtype, and the oral small molecule gives patients a new maintenance option after induction; eligibility is a decision for the treating oncologist.
来源：GSM·美国（原文链接）
图片来源：辉瑞公司全球总部（图卡替尼生产商Seagen为辉瑞子公司）。Photo: ajay_suresh, CC BY 2.0, via Wikimedia Commons
