Yoh Kiyotaka, Seto Takashi, Satouchi Miyako, Nishio Makoto, Yamamoto Noboru, Murakami Haruyasu, Nogami Naoyuki, Nosaki Kaname, Kohno Takashi, Tsuta Koji, Nomura Shogo, Ikeno Takashi, Wakabayashi Masashi, Sato Akihiro, Matsumoto Shingo, Goto Koichi
Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
Lung Cancer. 2021 May;155:40-45. doi: 10.1016/j.lungcan.2021.03.002. Epub 2021 Mar 10.
The LURET phase II study evaluated the efficacy and safety of the multikinase inhibitor vandetanib in patients with previously treatedRET-rearranged advanced non-small cell lung cancer (NSCLC). Among the eligible patients included in the primary analysis, the objective response rate met the primary endpoint (53 %, 90 % confidence interval [CI]: 31-74). Here, we report final survival outcomes of the LURET study.
Nineteen patients with previously treated RET-rearranged advanced NSCLC continuously received 300 mg of oral vandetanib daily. This final analysis provides updated data on progression-free survival (PFS), overall survival (OS) and safety. This study was registered with UMIN-CTR (number UMIN 000010095).
Among the 19 patients in the intention-to-treat population, 42 % had been heavily treated with 3 or more prior chemotherapy regimens. The median PFS was 6.5 months (95 % CI, 3.9-9.3) as determined by an independent radiology review committee. The median OS was 13.5 months (95 % CI, 9.8-28.1) and the overall survival rate at 12 months was 52.6 % (95 % CI 28.7-71.9). The most common adverse events were hypertension (84.2 %), diarrhea (78.9 %), and rash acneiform (63.2 %). Overall, 11 patients (57.9 %) had adverse events leading to a dose reduction, although the safety profile was consistent with that reported in previous studies.
Our results indicated that vandetanib enabled a prolonged and clinically meaningful PFS and OS in patients with previously treatedRET-rearranged advanced NSCLC at the updated final analysis. The safety profile was consistent with that reported in previous studies, although most of the patients experienced off-target adverse events besides RET.
LURET II期研究评估了多激酶抑制剂凡德他尼在既往接受过治疗的RET重排晚期非小细胞肺癌（NSCLC）患者中的疗效和安全性。在纳入初步分析的符合条件的患者中，客观缓解率达到了主要终点（53%，90%置信区间[CI]：31-74）。在此，我们报告LURET研究的最终生存结果。
19例既往接受过治疗的RET重排晚期NSCLC患者持续每日口服300mg凡德他尼。本次最终分析提供了无进展生存期（PFS）、总生存期（OS）和安全性的更新数据。本研究已在UMIN-CTR注册（编号UMIN 000010095）。
在意向性治疗人群的19例患者中，42%曾接受过3种或更多先前化疗方案的重度治疗。经独立放射学审查委员会确定，中位PFS为6.5个月（95%CI，3.9-9.3）。中位OS为13.5个月（95%CI，9.8-28.1），12个月时的总生存率为52.6%（95%CI 28.7-71.9）。最常见的不良事件为高血压（84.2%）、腹泻（78.9%）和皮疹样痤疮（63.2%）。总体而言，11例患者（57.9%）出现导致剂量减少的不良事件，尽管安全性与先前研究报告的一致。
我们的结果表明，在更新的最终分析中，凡德他尼使既往接受过治疗的RET重排晚期NSCLC患者的PFS和OS得以延长且具有临床意义。安全性与先前研究报告的一致，尽管大多数患者除了RET外还经历了脱靶不良事件。
