A Phase II Trial of Salirasib in Patients with Lung Adenocarcinomas with KRAS Mutations
A Phase II Trial of Salirasib in Patients with Lung Adenocarcinomas with KRAS Mutations
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DOI：
10.1097/jto.0b013e318223c099
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发表时间：
2011-08-01
影响因子：
20.4
通讯作者：
Ginsberg, Michelle S.
中科院分区：
文献类型：
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作者：
Riely, Gregory J.;Johnson, Melissa L.;Ginsberg, Michelle S.
简介：KRAS突变存在于30%的肺腺癌中。Salirasib阻止Ras膜结合，从而阻断所有Ras同种型的功能。这项II期研究确定了salirasib在晚期肺腺癌KRAS突变患者中的活性。方法：两组IIIB/IV期肺腺癌患者符合条件：既往接受化疗的KRAS突变肿瘤患者和接受初始治疗的吸烟史≥ 15包年的患者。Salirasib从35天周期的第1天至第28天口服给药。主要终点是10周时的非进展率。30例患者存在KRAS突变（23例患者既往接受过治疗，7/10例患者既往未接受过治疗）。在既往接受过治疗的患者中，7/23例（30%）在第10周时病情稳定，4/10例（40%）既往未接受过治疗的患者在第10周时病情稳定。无患者出现放射学部分缓解（观察率为0%，95%置信区间为0 - 12%）。中位总生存期未达到（>9个月）为以前未经治疗的患者，它是15个月的患者谁接受了以前的化疗。腹泻，恶心，疲劳是最常见的toxics.Conclusions：Salirasib在目前的剂量和时间表在治疗KRAS突变肺腺癌的活性不足，需要进一步评估。在一个研究中心成功招募了30名患有KRAS突变型肺腺癌的肿瘤患者，为期15个月，这表明针对肺癌中KRAS特异性基因型的药物试验是可行的。
Introduction: KRAS mutations are present in 30% of lung adenocarcinomas. Salirasib prevents Ras membrane binding thereby blocking the function of all Ras isoforms. This phase II study determined the activity of salirasib in patients with advanced lung adenocarcinomas with KRAS mutations.Methods: Two cohorts of patients with stage IIIB/IV lung adenocarcinoma were eligible: patients with tumors with KRAS mutations who were previously treated with chemotherapy and patients receiving initial therapy who had >= 15 pack-year smoking history. Salirasib was given orally from days 1 to 28 of a 35-day cycle. The primary end point was the rate of nonprogression at 10 weeks.Results: Thirty-three patients were enrolled. Thirty patients had KRAS mutations (23 patients who were previously treated and 7/10 patients who had no prior therapy). Of the previously treated patients, 7 of 23 (30%) had stable disease at 10 weeks, and 4 of 10 (40%) previously untreated patients had stable disease at 10 weeks. No patient had a radiographic partial response (0% observed rate, 95% confidence interval 0 -12%). The median overall survival was not reached (>9 months) for previously untreated patients and it was 15 months for patients who received prior chemotherapy. Diarrhea, nausea, and fatigue were the most common toxicities.Conclusions: Salirasib at the current dose and schedule has insufficient activity in the treatment of KRAS mutant lung adenocarci-noma to warrant further evaluation. The successful enrollment of 30 patients with tumors with KRAS mutant lung adenocarcinoma over 15 months at a single site demonstrates that drug trials directed at a KRAS-specific genotype in lung cancer are feasible.