Crombet Ramos Tania, Santos Morales Orestes, Dy Grace K, León Monzón Kalet, Lage Dávila Agustín
Research Direction, Center of Molecular Immunology, Havana, Cuba.
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Front Oncol. 2021 Jun 15;11:639745. doi: 10.3389/fonc.2021.639745. eCollection 2021.
Advanced non-small cell lung cancer (NSCLC) has faced a therapeutic revolution with the advent of tyrosine kinase inhibitors (TKIs) and immune checkpoints inhibitors (ICIs) approved for first and subsequent therapies. CIMAvax-EGF is a chemical conjugate between human-recombinant EGF and P64, a recombinant protein from , which induces neutralizing antibodies against EGF. In the last 15 years, it has been extensively evaluated in advanced NSCLC patients. CIMAvax-EGF is safe, even after extended use, and able to keep EGF serum concentration below detectable levels. In a randomized phase III study, CIMAvax-EGF increased median overall survival of advanced NSCLC patients with at least stable disease after front-line chemotherapy. Patients bearing squamous-cell or adenocarcinomas and serum EGF concentration above 870 pg/ml had better survival compared to control patients treated with best supportive care as maintenance, confirming tumors' sensitivity to the EGF depletion. This manuscript reviews the state-of-the-art NSCLC therapy and proposes the most promising scenarios for evaluating CIMAvax-EGF, particularly in combination with TKIs or ICIs. We hypothesize that the optimal combination of CIMAvax-EGF with established therapies can further contribute to transform advanced cancer into a manageable chronic disease, compatible with years of good quality of life.
随着酪氨酸激酶抑制剂（TKIs）和免疫检查点抑制剂（ICIs）被批准用于一线及后续治疗，晚期非小细胞肺癌（NSCLC）迎来了治疗革命。CIMAvax-EGF是一种人重组表皮生长因子（EGF）与P64的化学偶联物，P64是一种来自[具体来源未提及]的重组蛋白，它可诱导产生抗EGF的中和抗体。在过去15年里，它已在晚期NSCLC患者中得到广泛评估。CIMAvax-EGF即使长期使用也是安全的，并且能够使EGF血清浓度保持在可检测水平以下。在一项随机III期研究中，CIMAvax-EGF提高了一线化疗后至少病情稳定的晚期NSCLC患者的中位总生存期。与接受最佳支持治疗作为维持治疗的对照患者相比，患有鳞状细胞癌或腺癌且血清EGF浓度高于870 pg/ml的患者生存期更长，这证实了肿瘤对EGF耗竭的敏感性。本文综述了NSCLC治疗的最新进展，并提出了评估CIMAvax-EGF最有前景的方案，特别是与TKIs或ICIs联合使用时。我们假设CIMAvax-EGF与现有疗法的最佳联合可以进一步有助于将晚期癌症转变为可控制的慢性疾病，与多年的良好生活质量相兼容。
