Thoracic Oncology Unit, Instituto Nacional de Cancerología de México (INCan), Av. San Fernando No. 22, Col. Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico.
Experimental Oncology Laboratory, INCan, Av. San Fernando No. 22, Col. Sección XVI, Delegación Tlalpan, CP 14080, Mexico City, Mexico.
Target Oncol. 2016 Oct;11(5):619-629. doi: 10.1007/s11523-016-0425-x.
C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib.
Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF content was measured by ELISA before and 2 months after the start of treatment. HGF levels were assessed with the objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS). This trial was registered on ClinicalTrials.gov: NCT01542437.
Fifty patients (75 %) were EGFR mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9-18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5-28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients, respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44 %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR 0.31; p = 0.006) in all and EGFR mutated patients.
A reduction in serum HGF levels was associated with improved outcomes in patients treated with afatinib. These results suggest HGF might have a role as a mechanism of resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to prevent or reverse resistance particularly in EGFR mutated patients.
C-met 及其配体肝细胞生长因子（HGF）与 EGFR-TKIs 的耐药机制有关。在接受阿法替尼治疗的 NSCLC 患者中，HGF 被评估为反应的临床标志物。
66 例 IIIB/IV 期肺腺癌患者在任何一线化疗进展后接受阿法替尼 40mg/天治疗。通过 RT-PCR 评估 EGFR 突变和 HER2 状态。通过 FISH 评估 HER2 扩增。在治疗开始前和 2 个月时通过 ELISA 测量血清 HGF 含量。使用客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）评估 HGF 水平。该试验在 ClinicalTrials.gov 上注册：NCT01542437。
50 名患者（75%）为 EGFR 突变阳性。所有患者的缓解率为 59%，EGFR 突变患者的缓解率为 78%。所有患者和 EGFR 突变患者的中位 PFS 分别为 10[95%CI6.8-13.1]和 14.5 个月[10.9-18.9]。所有患者和 EGFR 突变患者的中位 OS 分别为 22.8[17.5-28.1]和 32.4 个月[18.3-46.6]。血清 HGF 水平降低的患者 ORR 改善（75%比 44%；p=0.011），PFS（15.1[2.9-27.3]比 6.5 个月[3.9-9.1]；p=0.005）和 OS（NR 比 14.5 个月[7.8-21.3]；p=0.007）。血清 HGF 水平降低是所有患者和 EGFR 突变患者 PFS（HR0.40；p=0.021）和 OS（HR0.31；p=0.006）延长的独立相关因素。
阿法替尼治疗患者血清 HGF 水平降低与改善结局相关。这些结果表明 HGF 可能作为 EGFR-TKIs 耐药的机制发挥作用。HGF 可能代表一种潜在的治疗靶点，可预防或逆转耐药，特别是在 EGFR 突变患者中。
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