J Cancer 2019; 10(25):6261-6268. doi:10.7150/jca.34677

Review

Immune-Checkpoint Inhibitors as the First Line Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

Yuqiao Chen1, Yuan Zhou1, Lu Tang1, Xiong Peng1, Hong Jiang2, Guo Wang3, Wei Zhuang1✉

1. Department of Thoracic Surgery, Xiangya Hospital of Central South University, 410008 Changsha, Hunan, People's Republic of China.
2. Department of Neurology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, People's Republic of China.
3. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People's Republic of China.

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Citation:
Chen Y, Zhou Y, Tang L, Peng X, Jiang H, Wang G, Zhuang W. Immune-Checkpoint Inhibitors as the First Line Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials. J Cancer 2019; 10(25):6261-6268. doi:10.7150/jca.34677. Available from http://www.jcancer.org/v10p6261.htm

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Abstract

Background: This meta-analysis aimed to explore if immunotherapy or chemotherapy alone or in combination is a better first line treatment strategy for advanced non-small cell lung cancer (NSCLC) patients.

Methods: Electronic databases including Google Scholar, PMC, PubMed, EMBASE, Scopus and the major conference proceedings were searched for relevant randomized controlled trials (RCTs) comparing outcomes of immune-checkpoint inhibitor combined with chemotherapy or immune-checkpoint inhibitor alone over chemotherapy alone in patients with advanced NSCLC without previous treatment. Study heterogeneity was assessed using the I2 test.

Results: A total of 14 RCTs including 8,081 treatment naïve advanced NSCLC patients were enrolled in this study. Our results showed that in comparison to chemotherapy alone, introducing immunotherapy into first-line chemotherapy has significant benefit in tumor response (RR, 1.27; 95% CI, 1.09 to 1.48), progression-free survival (PFS) (HR, -0.43; 95% CI, -0.56 to -0.31), and overall survival (OS) (HR, -0.30; 95% CI, -0.45 to -0.14) but with an increased risk of grade3 - 5 toxicity (RR, 1.11; 95% CI, 1.04 to 1.18). The pooled results of comparison of immune therapy alone with chemotherapy alone in selected patients with positive expression of Programmed Death-ligament (PD-L1) or with a high tumor mutational burden, demonstrated similar tumor response (RR, 1.13; 95% CI, 0.88 to 1.46), 3 - 5 grade toxicity (RR, 0.69; 95% CI, 0.40 to 1.19) and long-term outcomes, including OS (HR, -0.20; 95% CI, -0.43 to 0.03) and PFS (HR, -0.24; 95% CI, -0.61 to 0.14).

Conclusions: Our meta-analysis showed the superiority of combination therapy over monotherapy with chemotherapeutic agents in terms of tumor response, and long-term survival, but with an increased the 3 - 5 grade toxicity. And immune-checkpoint inhibitors alone showed similar tumor response, toxicity and long-term outcomes compared to platinum-based chemotherapy in selected patients.