Palumbo Giuliano, Esposito Giovanna, Carillio Guido, Manzo Anna, Montanino Agnese, Sforza Vincenzo, Costanzo Raffaele, Sandomenico Claudia, La Manna Carmine, Martucci Nicola, La Rocca Antonello, De Luca Giuseppe, Piccirillo Maria Carmela, De Cecio Rossella, Perrone Francesco, Totaro Giuseppe, Muto Paolo, Picone Carmine, Normanno Nicola, Morabito Alessandro
Department of Oncology, Ospedale S. Maria della Pietà, Casoria, 80026 Napoli, Italy.
Thoracic Medical Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, 80131 Napoli, Italy.
Explor Target Antitumor Ther. 2020;1(2):117-130. doi: 10.37349/etat.2020.00008. Epub 2020 Apr 28.
Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advanced non-small-cell lung cancer (NSCLC). In pretreated patients with advanced EGFR wild type NSCLC, bevacizumab plus erlotinib improved progression-free survival as second-line therapy in the BeTa study and as maintenance therapy in the ATLAS trial, although the benefit was modest and did not translate into an advantage in overall survival. Disappointing results were reported with oral VEGF inhibitors plus erlotinib in pretreated patients with EGFR wild type NSCLC. On the contrary, erlotinib plus bevacizumab or ramucirumab showed a clinically relevant improvement of progression-free survival in naïve patients with EGFR mutations, leading to the approval of these two regimens as first-line treatment of NSCLC patients with EGFR mutant tumors. Several clinical studies are evaluating the feasibility and activity of osimertinib plus bevacizumab or ramucirumab. However, limits that could affect its use in clinical practice are the need of an intravenous infusion for angiogenesis inhibitors, the increased incidence of treatment associated adverse events, the exclusion of patients with tumors located in central position or at risk of hemorrhage. The identification of predictive biomarkers is an important goal of research to optimize the combined use of these agents.
多项临床前研究表明，表皮生长因子受体（EGFR）抑制剂与血管生成抑制剂联合治疗可能有益，这两种药物对晚期非小细胞肺癌（NSCLC）患者均有效。在既往接受过治疗的EGFR野生型晚期NSCLC患者中，在BeTa研究中，贝伐单抗联合厄洛替尼作为二线治疗以及在ATLAS试验中作为维持治疗可改善无进展生存期，尽管获益不大且未转化为总生存期的优势。在既往接受过治疗的EGFR野生型NSCLC患者中，口服VEGF抑制剂联合厄洛替尼的结果令人失望。相反，在初治的EGFR突变患者中，厄洛替尼联合贝伐单抗或雷莫西尤单抗显示无进展生存期有临床意义的改善，这导致这两种方案被批准作为EGFR突变肿瘤NSCLC患者的一线治疗。多项临床研究正在评估奥希替尼联合贝伐单抗或雷莫西尤单抗的可行性和活性。然而，可能影响其在临床实践中应用的局限性包括血管生成抑制剂需要静脉输注、治疗相关不良事件的发生率增加、排除肿瘤位于中央位置或有出血风险的患者。确定预测生物标志物是优化这些药物联合使用的重要研究目标。
