Abstract：
Combination of anti-EGFR monoclonal antibodies or immune checkpoint inhibitors with TKIs has shown minimal benefit in EGFR mutant (EGFR-mut) NSCLC patients. Consequently, new combination approaches are needed.
The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients. EGFR status and mutations in liquid biopsies were determined by reverse transcriptase-polymerase chain reaction; serum biomarkers by ELISA and Western blotting analysis.
The assay enrolled 23 patients, 21 completed the anti-EGF immunization phase. Treatment was well tolerated and no serious adverse events (SAEs) related to the anti-EGF vaccine were reported. Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8). Among the 21 patients completing the immunization phase, PFS was 17.5 months (95% CI = 12.0-23.0) and OS 26.9 months (95% CI = 24.6-NR). At the end of the immunization phase, all 21 patients showed high serum titers of anti-EGF antibodies, while EGF levels had decreased significantly. Finally, treatment with fully immunized patient\'s sera inhibited the EGFR pathway in tumor cells growing in vitro.
Combination treatment with an anti-EGF vaccine is well tolerated; induces a sustained immunogenic effect and might enhance the clinical efficacy of EGFR TKIs.
The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients. EGFR status and mutations in liquid biopsies were determined by reverse transcriptase-polymerase chain reaction; serum biomarkers by ELISA and Western blotting analysis.
The assay enrolled 23 patients, 21 completed the anti-EGF immunization phase. Treatment was well tolerated and no serious adverse events (SAEs) related to the anti-EGF vaccine were reported. Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8). Among the 21 patients completing the immunization phase, PFS was 17.5 months (95% CI = 12.0-23.0) and OS 26.9 months (95% CI = 24.6-NR). At the end of the immunization phase, all 21 patients showed high serum titers of anti-EGF antibodies, while EGF levels had decreased significantly. Finally, treatment with fully immunized patient\'s sera inhibited the EGFR pathway in tumor cells growing in vitro.
Combination treatment with an anti-EGF vaccine is well tolerated; induces a sustained immunogenic effect and might enhance the clinical efficacy of EGFR TKIs.
摘要：
抗EGFR单克隆抗体或免疫检查点抑制剂与TKI的组合在EGFR突变（EGFR-mut）NSCLC患者中显示出最小的益处。因此,需要新的组合方法。
EPICAL是一只手臂,评估安全性的1b期研究，在晚期EGFR-mut患者中，一线阿法替尼联合抗EGF疫苗接种的耐受性和抗肿瘤活性。通过逆转录酶-聚合酶链反应确定液体活检中的EGFR状态和突变；通过ELISA和Western印迹分析确定血清生物标志物。
该试验招募了23名患者，21完成了抗EGF免疫阶段。治疗耐受性良好，未报告与抗EGF疫苗相关的严重不良事件（SAE）。客观反应和疾病控制率分别为78.3%（95CI=53.6-92.5）和95.7%（95CI=78.1-99.9），分别。在中位随访24.2个月后，中位无进展生存期(PFS)为14.8个月(95%CI=9.5~20.1),中位总生存期(OS)为26.9个月(95%CI=23.0~30.8).在完成免疫阶段的21名患者中，PFS为17.5个月（95%CI=12.0-23.0），OS为26.9个月（95%CI=24.6-NR）。在免疫阶段结束时，所有21例患者均表现出高血清滴度的抗EGF抗体，而EGF水平显著下降。最后,用完全免疫的患者血清治疗抑制了体外生长的肿瘤细胞中的EGFR通路。
与抗EGF疫苗的组合治疗具有良好的耐受性;诱导持续的免疫原性作用,并且可能增强EGFRTKIs的临床功效。
EPICAL是一只手臂,评估安全性的1b期研究，在晚期EGFR-mut患者中，一线阿法替尼联合抗EGF疫苗接种的耐受性和抗肿瘤活性。通过逆转录酶-聚合酶链反应确定液体活检中的EGFR状态和突变；通过ELISA和Western印迹分析确定血清生物标志物。
该试验招募了23名患者，21完成了抗EGF免疫阶段。治疗耐受性良好，未报告与抗EGF疫苗相关的严重不良事件（SAE）。客观反应和疾病控制率分别为78.3%（95CI=53.6-92.5）和95.7%（95CI=78.1-99.9），分别。在中位随访24.2个月后，中位无进展生存期(PFS)为14.8个月(95%CI=9.5~20.1),中位总生存期(OS)为26.9个月(95%CI=23.0~30.8).在完成免疫阶段的21名患者中，PFS为17.5个月（95%CI=12.0-23.0），OS为26.9个月（95%CI=24.6-NR）。在免疫阶段结束时，所有21例患者均表现出高血清滴度的抗EGF抗体，而EGF水平显著下降。最后,用完全免疫的患者血清治疗抑制了体外生长的肿瘤细胞中的EGFR通路。
与抗EGF疫苗的组合治疗具有良好的耐受性;诱导持续的免疫原性作用,并且可能增强EGFRTKIs的临床功效。
