Locati Laura D, Licitra Lisa, Agate Laura, Ou Sai-Hong I, Boucher Andree, Jarzab Barbara, Qin Shukui, Kane Madeleine A, Wirth Lori J, Chen Connie, Kim Sinil, Ingrosso Antonella, Pithavala Yazdi K, Bycott Paul, Cohen Ezra E W
Head and Neck Medical Oncology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
Cancer. 2014 Sep 1;120(17):2694-703. doi: 10.1002/cncr.28766. Epub 2014 May 20.
In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed.
Patients (N = 52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters, and patient-reported outcomes assessed with the MD Anderson Symptom Inventory questionnaire.
The overall ORR was 35% (18 partial responses), and 18 patients had stable disease for ≥16 weeks. The median PFS was 16.1 months, and the median OS was 27.2 months. All-causality, grade ≥3 adverse events (>5%) were fatigue, dyspnea, diarrhea, decreased weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Patients who had greater axitinib exposure had a longer median PFS. Quality of life was maintained during treatment with axitinib, and no significant deterioration in symptoms or interference in daily life caused by symptoms, assessed on MD Anderson Symptom Inventory subscales, were observed.
Axitinib has activity and a manageable safety profile while maintaining quality of life, and it represents an additional treatment option for patients with advanced thyroid cancer.
在先前的一项2期试验中，阿昔替尼对晚期甲状腺癌患者有效且耐受性良好。在这项第二项2期试验中，对该人群进一步评估了阿昔替尼的疗效和安全性，并评估了药代动力学/药效学关系以及患者报告的结局。
52例转移性或不可切除的局部晚期髓样或分化型甲状腺癌患者，这些患者对碘-131难治或不适用，接受阿昔替尼起始剂量5mg，每日两次。主要终点是客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）、安全性、药代动力学参数以及使用MD安德森症状量表问卷评估的患者报告结局。
总体ORR为35%（18例部分缓解），18例患者疾病稳定≥16周。中位PFS为16.1个月，中位OS为27.2个月。所有原因导致的≥3级不良事件（>5%）为疲劳、呼吸困难、腹泻、体重减轻、肢体疼痛、高血压、食欲减退、手足红斑感觉异常、低钙血症和肌痛。阿昔替尼暴露量较高的患者中位PFS更长。在阿昔替尼治疗期间生活质量得以维持，在MD安德森症状量表各分量表上评估，未观察到症状有显著恶化或症状对日常生活造成干扰。
阿昔替尼具有活性且安全性可控，同时维持生活质量，它是晚期甲状腺癌患者的又一种治疗选择。
