Abstract
Background The prognosis of patients with extensive-stage small cell lung cancer (SCLC) is poor. Adding an immune checkpoint inhibitor (ICI) to chemotherapy may exert a synergistic effect and improve survival outcomes. However, for treatment-naive extensive-stage SCLC patients, the efficacy of immunotherapy in combination with cytotoxic chemotherapy remains controversial. Objective To evaluate the benefits and risks of the combination of immunotherapy and chemotherapy and to assess the comparative effectiveness of different first-line treatment strategies for extensive-stage SCLC. Methods PubMed, Web of Science, EMBASE, and Cochrane Library were searched for randomized clinical trials studying different immunotherapeutics for patients with previously untreated extensive-stage SCLC up to Feb 16, 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. Results We identified 141 published records, and 4 studies (comprising 2202 patients) were included in the analysis. Immunotherapy (including ipilimumab, atezolizumab, and durvalumab) plus chemotherapy was associated with better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.93; risk ratio (RR) 0.90, 95% CI 0.81–1.00) and PFS (HR: 0.81, 95% CI 0.74–0.88; RR 0.96, 95% CI 0.93–0.99) than placebo plus chemotherapy. The addition of immunotherapy to chemotherapy showed similar improvement in ORR, DCR, and adverse events versus placebo plus chemotherapy. On the surface under the cumulative ranking (SUCRA) analysis, the anti-PD-L1 agent, atezolizumab, had the highest likelihood of achieving improved OS (93.4%) and PFS (95.0%). Conclusion In the first-line setting, combining immunotherapy with chemotherapy is better than standard chemotherapy in terms of OS and PFS. Across the eligible studies, PD-L1 inhibitors might be preferred. Further explorations of more ICIs in the first-line treatment for extensive-stage SCLC patients should be needed.
Highlights
Small cell lung cancer represents over 10% of all lung cancer [1]
Two authors reviewed the records and selected the eligible studies independently. e inclusion criteria were as follows: (1) prospective randomized controlled clinical studies were published in the form of full papers; (2) efficacy and safety data in the studies were extractable; (3) enrolled patients were newly diagnosed as extensive-stage small cell lung cancer (SCLC) and previously untreated; and (4)
On surface under the cumulative ranking (SUCRA) analysis, we found that atezolizumab was ranked highest in terms of overall survival (OS) (93.4%) and progression-free survival (PFS) (95.0%), while durvalumab was ranked
Summary
Small cell lung cancer represents over 10% of all lung cancer [1]. Extensive-stage SCLC is defined as the cancer cells which extend beyond one hemithorax at the time of initial diagnosis. Platinum-based combination chemotherapy is the current first-line standard-of-care for SCLC. The first-line cytotoxic chemotherapy results in an overall response rate with 60%–80%, the majority of extensive-stage SCLC patients suffers disease progression. Journal of Oncology or relapse within months, and the 5-year survival rate is only about 2% [2]. Immunotherapy has revolutionized the treatment strategies for lung cancer. SCLC has a high rate of gene mutation that indicates SCLC cells may be immunogenic and might respond to immune-related treatments [3,4,5]
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