P48.18 Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Systematic Review and Meta-Analysis

Abstract

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with early metastatic potential. Standard of care with platinum-etoposide chemotherapy has not changed in 30 years. Immune checkpoint inhibitors (ICI) have recently demonstrated significant improvement in non-small cell lung cancer (NSCLC) patients. There is evidence for increased benefit of ICI in mutagenic cancers, such as SCLC, caused by exposure to carcinogens (i.e. smoking). There are now several studies that report improved progression free survival (PFS) and overall survival (OS) with combined ICI and chemotherapy in ES-SCLC. We aimed to assess the magnitude of the survival benefit of combined chemo-ICI in the first line systemic treatment of ES-SCLC as compared to standard of care chemotherapy. MEDLINE, EMBASE and the Cochrane library were systematically searched, along with abstracts from relevant major conferences (i.e. ASCO, ESMO, WCLC). We searched databases between January 1, 2010 and June 10, 2020 and limited the search of relevant meeting and conference proceedings to 2018 to 2020. Studies were included if they met the following criteria: randomized controlled trials, patients with untreated ES-SCLC treated with combined chemo-ICI as compared to standard of care chemotherapy. Any chemo-ICI pairings were eligible including PD-1 inhibitors, PD-L1 inhibitors and CTLA-4 inhibitors, combined with platinum-etoposide or platinum-paclitaxel chemotherapy. Trials were excluded if patients were being treated in the second or further line. Relevant outcomes of interest were survival outcomes (PFS and OS), measures of response (objective response rate (ORR), duration of response (DoR)), and toxicity (Grade 1-4 toxicity, Grade 3-4 toxicity). A total of 2705 studies and abstracts were identified in our initial search, with 6 studies (33 publications) included in the final analysis. PFS was significantly improved for patients randomized to chemo-ICI compared with chemotherapy alone (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.75-0.87). Similarly, OS was significantly improved (HR 0.82, 95% CI 0.76-0.89). The between-study heterogeneity was low (I2 0%) for both outcomes. A prespecified subgroup analysis demonstrated no evidence of any significant differential effect between PD-1/PD-L1 inhibitors and CTLA-4 inhibitors. The pooled ORR as expressed as a risk ratio comparing chemo-ICI with chemotherapy alone was 1.04 (95% CI 0.98-1.10) and the pooled duration of response demonstrated a mean difference of 0.09 months (95% CI -0.13-0.32) in favor of chemo-ICI. There were no significant increases in either all grade adverse events (pooled risk ratio of 1.03, 95% CI 1.01-1.06), or grade 3-4 adverse events (risk ratio of 1.06, 95% CI 0.99-1.13). Multiple trials have assessed the efficacy of combined chemo-ICI regimens. They consistently demonstrate survival improvements in both PFS and OS with combined chemo-ICI. This review demonstrates an approximate18% risk reduction in death, and 19% risk reduction in disease progression. The pooled analysis suggests a minimal increase in toxicity with chemo-ICI regimens though clinically relevant toxicity (Grade 3-4 toxicity) crossed null. Chemo-ICI appears to offer survival benefit with potentially equivalent toxicity profile in the setting of first line ES-SCLC regardless of the class of ICI.