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Whether primary tumor surgery is better than no surgery in patients with de novo stage IV breast cancer remains controversial. This study combined prospective clinical trials and a multicenter cohort to evaluate the impact of locoregional surgery in de novo stage IV breast cancer. The GRADE approach was used to assess the quality of evidence in meta-analysis, and propensity score matching analysis was used in the cohort study. This study was registered with PROSPERO CRD42016043766 and ClinicalTrials.gov NCT04456855. A total of 1110 patients from six trials and 353 patients from the cohort study were included. The meta-analysis showed that compared with no surgery, locoregional surgery did not prolong overall survival (hazard ratio [HR] = 0.90, P = 0.40; moderate-quality) but had a significantly longer locoregional progression-free survival (HR = 0.23, P

Background: The clinical benefit of chemotherapy or endocrine therapy maintenance in patients with metastatic breast cancer (MBC) after first-line chemotherapy, specifically hormone receptor (HR) positive MBC patients remain inconclusive. This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in MBC patients. Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matched analysis of multicentre cohort study in China were evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. The GRADE approach was used to assess quality of evidence in meta-analysis. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Findings: A total of 2,867 patients from 15 RCTs and 760 patients from multicentre cohort were included. The results from meta-analysis showed that chemotherapy maintenance significantly improved PFS (hazard ratio [HR], 0·63; 95% confidence interval (CI) 0·54-0·73; P 0·05). Additionally, treatment effect sizes were greater for OS than for PFS, and a moderate correlation between PFS and OS was identified. Interpretation: This study provided a high evidence for PFS and OS benefits of longer first-line chemotherapy and endocrine therapy maintenance in MBC patients, and there were no difference efficacy between chemotherapy and endocrine therapy maintenance for HR-positive patients. We also suggested that both PFS and OS should be evaluated to determine the effectiveness of maintenance therapy in future clinical trials. Trial Registration: This study is registered with PROSPERO Identifier: CRD42017071858, and ClinicalTrials.gov Identifier: NCT04258163. Funding Statement: This study was supported by grant 2020ZX09201021 from the National Science and Technology Major Project, grant YXRGZN201902 from the Medical Artificial Intelligence Project of Sun Yat-Sen Memorial Hospital, grants 81572596, 81972471, U1601223, 82073408, 81802656, and 82071754 from the National Natural Science Foundation of China, grant 2017A030313828 from the Natural Science Foundation of Guangdong Province, grant 201704020131 from the Guangzhou Science and Technology Major Program, grant 2017B030314026 from the Guangdong Science and Technology Department, grant 2018007 from the Sun Yat-Sen University Clinical Research 5010 Program, grant SYS-C-201801 from the Sun Yat-Sen Clinical Research Cultivating Program, and A2020558 from the Medical Scientific Research Foundation of Guangdong Province. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The study protocol was approved by the ethics committee of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

Purpose To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). Methods We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766. Results The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63–0.75, P

1082Background: Current guidelines lack definitive evidences about the relative benefits of locoregional surgery for the primary tumor in de novo stage IV breast cancer. The aim of this study was t...

e16129Background: The role of immune biomarkers in predicting benefits of hepatocellular carcinoma (HCC) was still controversial. We was aimed to investigate the prognostic value of immune biomarke...

e13082Background: The relative clinical outcomes associated with recommended first-line single-agent chemotherapy in metastatic breast cancer (MBC) is not clearly established. We aimed to comprehen...

4040Background: The role of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACR) in patients with oesophageal carcinoma continues to be debated. This study aimed to assess the comparative eff...

e16125Background: The role of adjuvant interferon, tumor vaccines or cellular immunotherapies in patients with hepatocellular carcinoma (HCC) continues to be debated. This study aimed to assess the...

1088Background: Current guidelines lack definitive evidence regarding the clinical outcomes associated with different maintenance strategies for metastatic breast cancer (MBC). We aimed to investig...

e21056Background: We previously identified that immunotherapy including immune checkpoint inhibitor (ICI), tumor vaccine (TV) and cellular immunotherapy (CIM) improved overall survival (OS) and pro...

168 Background: Treatment with immune checkpoint inhibitors is becoming the standard of care for patients and it was approved for the treatment of non-small-cell lung cancer (NSCLC) growing at a rapid pace. However, selecting patients who are appropriate for therapy and which therapeutic strategies to use can be challenging. Methods: We searched for randomized clinical trials (RCTs) investigating immune checkpoint inhibitors versus observation in patients with advanced NSCLC until September 2017. Overall survival (OS) and progression-free survival (PFS) were pooled by meta-analysis. The GRADE system was used to describe the quality of evidence. Results: The analysis included 11 trials with 5,538 unique patients. High- to moderate-quality evidence indicated that immune checkpoint inhibitors extended NSCLC survival and PFS, expressed as hazard ratios (HRs) (OS: 0.79, P = 0.000; PFS: 0.78, P = 0.000). High- to moderate-quality evidence revealed prolonged OS and PFS were similar across preplanned subgroups in patients with squamous (0.77, P = 0.000 and 0.74, P = 0.001) or nonsquamous disease (0.76, P = 0.003 and 0.73, P = 0.041), EGFR wild-type positive status (0.67, P = 0.000 and 0.59, P = 0.010), current or former smokers (OS: 0.83, P = 0.009), and male (0.79, P = 0.000 and 0.67, P = 0.023). Increasing improvement in OS was associated with increasing PD-L1 expression (TC3 or IC3 HR 0.54, P = 0.000; TC2/3 or IC2/3 HR 0.62, P = 0.007; TC1/2/3 or IC1/2/3 HR 0.64, P = 0.000; TC0 and IC0 HR 0.72, P = 0.017; high- to moderate-quality evidence). In exploratory subgroup analysis suggest that there was advantageous of immune checkpoint inhibitors in previous definitive chemotherapy compared with chemoradiotherapy, with concurrent administration of chemotherapy (OS as HR: P = 0.001, P = 0.006, respectively). Conclusions: This large and comprehensive analysis produced firm evidence that immune checkpoint inhibitors extended advanced NSCLC survival and PFS, while in some patients with EGFR wild-type positive status, current or former smokers, male and higher PD-L1 expression had substantial benefit. The benefits from therapy appear to be influenced by preceding definitive therapy and concurrent chemotherapy.

165 Background: Checkpoint inhibitors, tumor vaccines or cellular immunotherapies demonstrated prolonged survival versus placebo or observation in several randomized clinical trials (RCTs) of patients with advanced non-small-cell lung cancer (NSCLC). We aimed to clarify the benefits of imunotherapy by a meta-analysis of RCTs data. Methods: We searched for RCTs investigating immunotherapy versus placebo or observation in patients with advanced NSCLC. Overall survival (OS) and progression-free survival (PFS) were calculated as combined hazard ratios (HRs). The quality of the evidence was evaluated with the GRADE framework. Results: Overall, 23 RCTs including a total of 8,956 patients were identified (5,142 patients in the immunotherapy group and 3,814 in the placebo or observation group). High- to moderate-quality evidence indicated that immunotherapy prolonged OS (HR = 0.79, 95% confidence interval (CI) 0.75 to 0.84, P < 0.0001) and PFS (HR = 0.80, 95% CI 0.73 to 0.88, P < 0.0001). In subgroup analysis, high- to moderate-quality evidence revealed immunotherapy extended NSCLC survival and PFS in tumor vaccines (HR, 0.84, 95% CI 0.76 to 0.92 and 0.86, 95% CI 0.78 to 0.94 for OS and PFS, respectively), checkpoint inhibitors (0.77, 95% CI 0.72 to 0.83 and 0.78, 95% CI 0.68 to 0.90, respectively), maintenance therapy (0.77, 95% CI 0.71 to 0.83 and 0.78, 95% CI 0.66 to 0.91, respectively), first-line therapy (0.89, 95% CI 0.80 to 0.98 and 0.76, 95% CI 0.64 to 0.91, respectively), previous definitive chemotherapy (0.72, 95% CI 0.67 to 0.78 and 0.87, 95% CI 0.79 to 0.95, respectively), and concurrent chemotherapy (0.87, 95% CI 0.80 to 0.95 and 0.84, 95% CI 0.77 to 0.91, respectively). There was a benefit of immunotherapy in previous definitive chemotherapy compared with chemoradiotherapy and with concurrent administration of chemotherapy (OS as HR: P = 0.002 and P = 0.006, respectively). Conclusions: This analysis provides strong evidence for OS and PFS benefit of immunotherapy in patients with advanced NSCLC, particularly in those receiving tumor vaccines, checkpoint inhibitors, maintenance and first-line therapy, previous definitive chemotherapy, and with concurrent chemotherapy.

194 Background: Immune checkpoint inhibitors selection in advanced melanoma is complicated further, with choices among anti-CTLA4 or anti-PD-1 therapeutic antibodies options. We aimed to evaluate the clinical benefits of immune checkpoint inhibitors for discussing evidence-based treatment strategies by a meta-analysis of randomized clinical trials (RCTs) data. Methods: We searched for RCTs investigating immune checkpoint inhibitors in patients with advanced melanoma until September 2017. Hazard ratios (HRs) was estimated for overall survival (OS) and progression-free survival (PFS). The quality of the evidence was evaluated with the GRADE framework. Results: Overall, 18 RCTs including a total of 8,917 patients were identified. Immune checkpoint inhibitors versus placebo or observation prolonged PFS (HR = 0.59, 95% confidence interval (CI) 0.44 to 0.78, P < 0.0001) and OS (HR = 0.77, 95% CI 0.72 to 0.84, P < 0.0001). The combination immunotherapy had significantly higher benefit than monotherapy for PFS (HR = 0.75, 95% CI 0.61 to 0.92, P = 0.005) and OS (HR = 0.70, 95% CI 0.61 to 0.79, P < 0.0001). Treatment with anti-PD-1 monoclonal antibody was associated with improved PFS (HR = 0.61, 95% CI 0.59 to 0.69, P < 0.0001) and OS (HR = 0.66, 95% CI 0.58 to 0.77, P < 0.0001) compared with anti-CTLA-4 monoclonal antibody. According to BRAF status analysis, there was a PFS benefit of immune checkpoint inhibitors versus placebo or observation (mutant, HR = 0.58, 95% CI 0.35 to 0.96, P = 0.035; wild–type, HR = 0.52, 95% CI 0.43 to 0.69, P = 0.001), anti-PD-1 outperformed anti-CTLA-4 checkpoint inhibitor (mutant, PFS HR = 0.64, 95% CI 0.51 to 0.79, P < 0.0001; wild–type, PFS HR = 0.58, 95% CI 0.47 to 0.71, P < 0.0001); and combination compared with single-agent immunotherapy (mutant, HR = 0.38, 95% CI 0.15 to 0.98, P = 0.046; wild–type, HR = 0.40, 95% CI 0.23 to 0.69, P = 0.001). Conclusions: This analysis provides an evidence that immune checkpoint inhibitors enhanced OS and PFS in patients with advanced melanoma, as well as combination immunotherapy and anti-PD-1 monoclonal antibody appear to be clinically beneficial option preference.

e12511 Background: To investigate the efficacy and safety of doublet vs. single-agent chemotherapy (CT) plus trastuzumab as first-line treatments for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). Methods: We searched for randomized clinical trials (RCTs) that investigated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcome measures for this analysis included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Meta-analyses and trial sequential analyses (TSA) were conducted. The study quality was evaluated using the GRADE framework. The PROSPERO registry number is CRD42016043766. Results: The results from four RCTs that included 1,044 participants were pooled. Moderate-quality evidence indicated that doublet CT+H better correlated with prolonged PFS (hazard ratio [HR] = 0.69, 95% confidence interval (CI) 0.63 to 0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88 to 0.92, P < 0.0001) than did single-agent CT+H; however, moderate-quality evidence indicated there was no significant difference between the two drug regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98 to 1.17, P = 0.157), as confirmed by TSA, which indicated that the cumulative Z-curve entered the futility area. There was moderate-quality evidence that the treatment-related grade 3 to 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000; number needed to treat to harm (NNTH) = 20), nausea/vomiting (RR = 4.26, P = 0.002; NNTH = 25), diarrhea (RR = 2.81, P = 0.002; NNTH = 25), and stomatitis (RR = 5.02, P= 0.003; NNTH = 25) were more frequent with doublet CT+H than single-agent CT+H. Conclusions: Doublet CT+H is associated with longer PFS and OS than single-agent CT+H when used as a first-line therapy for HER2-positive MBC.

566 Background: Existing guidelines lack clear recommendations for the role of locoregional treatment for the primary tumor in women with stage IV breast cancer. We aimed to compare the effectiveness of locoregional surgery with no surgery of the primary tumour in stage IV breast cancer patients. Methods: Eligible studies were randomized clinical trials (RCTs) that investigated the effect of locoregional surgery versus no surgery of the primary tumour in stage IV breast cancer patients. The primary outcome was overall survival (OS), measured as hazard ratios (HRs). Secondly outcomes included 2-year and 3-year OS, expressed as odds ratios (ORs). Meta-analyses and trial sequential analysis (TSA) were conducted. Quality was evaluated using the GRADE. Results: Data were included from four RCTs involving 767 participants, including 377 who underwent locoregional surgery and 390 who with no surgery. The median follow-up was 28.6 months (95% confidence interval (CI) 24.1 to 33.9). In a meta-analysis of these trials, the low-quality evidence indicated that locoregional surgery versus no surgery did not significantly affect OS (HR = 0.87, 95% CI 0.59 to 1.29, P = 0.490), 2-year OS (OR = 1.23, 0.66 to 2.30, P = 0.510), or 3-year OS (OR = 1.08, 0.94 to 1.25, P = 0.263). TSA showed that more trials were needed before reliable conclusions could be drawn regarding in both 2-year and 3-year OS. Across the subgroup analysis of OS, we found the moderate-quality evidence that locoregional surgery followed by chemotherapy versus chemotherapy alone resulted into a significantly improved survival (HR = 0.65, 95% CI 0.49–0.87, P = 0.004); but no statistically significant difference was identified in term of response to chemotherapy with or without locoregional surgery (HR = 1.06, 95% CI 0.83–1.36, P = 0.632). Conclusions: The current evidence suggests that locoregional surgery followed by chemotherapy, compared with chemotherapy alone, was beneficial for prolonging OS in patients with stage IV breast cancer, but surgery did not impact OS among patients who have responded to chemotherapy.