Guangzhou Municipal Key Laboratory of Allergy and Clinical Immunology, Allergy Research Branch of the State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
PLoS One. 2012;7(3):e32695. doi: 10.1371/journal.pone.0032695. Epub 2012 Mar 5.
Lung cancer is one of the leading causes of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy has yielded no consistent benefit to date for those patients. Assessing the objective efficacy and safety of immunotherapy for advanced NSCLC patients will help to instruct the future development of immunotherapeutic drugs.
We performed a meta-analysis of 12 randomized controlled trials including 3134 patients (1570 patients in the immunotherapy group and 1564 patients in the control group) with histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed with efficacy end points regarding overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and total effective rate. Overall unstratified OS, PFS, PR, and total effective rate were significantly improved in advanced NSCLC patients in the immunotherapy group (P = 0.0007, 0.0004, 0.002, 0.003, respectively), whereas CR was not improved (P = 0.97). Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant. Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events.
Immunotherapy works efficiently on advanced NSCLC patients. Of several immunotherapies, mAb therapy may be a potential immunotherapy for advanced NSCLC patients, and become a standard complementary therapeutic approach in the future if the issues concerning toxicity and allergenicity of mAbs have been overcome.
肺癌是全球癌症死亡的主要原因之一。非小细胞肺癌(NSCLC)约占所有肺癌的 85%。迄今为止,免疫疗法并未给此类患者带来一致的获益。评估免疫疗法治疗晚期 NSCLC 患者的客观疗效和安全性,有助于指导免疫治疗药物的未来发展。
我们对 12 项随机对照试验进行了荟萃分析,纳入了 3134 例组织学确诊的 IIIA、IIIB 或 IV 期 NSCLC 患者(免疫治疗组 1570 例,对照组 1564 例)。分析的疗效终点包括总生存期(OS)、无进展生存期(PFS)、完全缓解(CR)、部分缓解(PR)和总有效率。免疫治疗组晚期 NSCLC 患者的总体未分层 OS、PFS、PR 和总有效率显著提高(P = 0.0007、0.0004、0.002、0.003),而 CR 未提高(P = 0.97)。亚组分析显示,与对照组相比,单克隆抗体(mAb)免疫疗法显著改善了晚期 NSCLC 患者的 PFS、PR 和总有效率,并表现出改善 OS 的趋势,但有一种不良事件明显占优势。与对照组相比,疫苗亚组在严重不良事件方面无显著差异,而细胞因子免疫疗法则显著导致了三种严重不良事件。
免疫疗法对晚期 NSCLC 患者有效。在几种免疫疗法中,mAb 疗法可能是晚期 NSCLC 患者的一种有潜力的免疫疗法,如果克服了 mAb 的毒性和变应原性问题,它可能成为未来的一种标准辅助治疗方法。