Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings
Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings
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DOI：
10.1093/annonc/mdt231
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发表时间：
2013-09-01
影响因子：
50.5
通讯作者：
Arnold, D.
中科院分区：
文献类型：
--
作者：
Kubicka, S.;Greil, R.;Arnold, D.
ML18147 评估了在标准一线含贝伐单抗治疗后进展的转移性结直肠癌 (mCRC) 患者继续贝伐单抗联合二线化疗的情况。根据肿瘤 Kirsten 大鼠肉瘤病毒癌基因 (KRAS) 状态评估结果是一项探索性分析。 KRAS 数据是从当地实验室（使用其既定方法）和/或中心实验室（突变特异性 Scorpion 扩增-难治性突变系统）收集的。没有对多重性进行调整；分析无法检测出统计学上显着的差异。在 820 名患者中，616 名 (75%) 拥有明确的 KRAS 数据； 316 例 (51%) 患有 KRAS 野生型肿瘤，300 例 (49%) 患有突变型 KRAS 肿瘤。贝伐珠单抗加化疗的中位无进展生存期 (PFS) 为 6.4 个月，化疗为 4.5 个月 [P < 0.0001；心率=0.61；野生型 KRAS 的 95% 置信区间 (CI)：0.49-0.77]，突变型 KRAS 的 95% 置信区间 (CI) 分别为 5.5 个月和 4.1 个月（P = 0.0027；HR = 0.70；95% CI：0.56-0.89）。野生型 KRAS 的中位总生存期 (OS) 分别为 15.4 个月和 11.1 个月（P = 0.0052；HR = 0.69；95% CI：0.53-0.90）；突变型 KRAS 的中位总生存期（OS）分别为 10.4 个月和 10.0 个月（P = 0.4969；HR = 0.92；95% CI：0.71-1.18）克拉斯。在两项分析中，均未观察到 KRAS 状态导致的治疗相互作用（PFS，P = 0.4436；OS，P = 0.1266）。首次进展后的贝伐珠单抗是接受贝伐珠单抗加标准一线化疗治疗的 mCRC 患者的一种选择，与 KRAS 状态无关。
ML18147 evaluated continued bevacizumab with second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) progressing after the standard first-line bevacizumab-containing therapy.Evaluating outcomes according to tumor Kirsten rat sarcoma virus oncogene (KRAS) status was an exploratory analysis. KRAS data were collected from local laboratories (using their established methods) and/or from a central laboratory (mutation-specific Scorpion amplification-refractory mutation system). No adjustment was made for multiplicity; analyses were not powered to detect statistically significant differences.Of 820 patients, 616 (75%) had unambiguous KRAS data; 316 (51%) had KRAS wild-type tumors and 300 (49%) had mutant KRAS tumors. The median progression-free survival (PFS) was 6.4 months for bevacizumab plus chemotherapy and 4.5 months for chemotherapy [P < 0.0001; HR = 0.61; 95% confidence interval (CI): 0.49-0.77] for wild-type KRAS and 5.5 and 4.1 months, respectively (P = 0.0027; HR = 0.70; 95% CI: 0.56-0.89) for mutant KRAS. The median overall survival (OS) was 15.4 and 11.1 months, respectively (P = 0.0052; HR = 0.69; 95% CI: 0.53-0.90) for wild-type KRAS and 10.4 versus 10.0 months, respectively (P = 0.4969; HR = 0.92; 95% CI: 0.71-1.18) for mutant KRAS. In both analyses, no treatment interaction by KRAS status was observed (PFS, P = 0.4436; OS, P = 0.1266).Bevacizumab beyond first progression represents an option for patients with mCRC treated with bevacizumab plus standard first-line chemotherapy, independent of KRAS status.