Pooled Median Overall Survival Research Articles

A meta-analysis of overall survival and response in metastatic adrenocortical carcinoma: A review of 23 prospective trials of 880 patients.

4 Background: Metastatic adrenocortical carcinoma (mACC) is a rare, aggressive tumour of the adrenal gland, with historically poor survival and limited established treatment modalities. The aim of this study was to systematically search for and analyse all prospective trials for mACC to establish benchmark response and survival outcomes. The study was registered on PROSPERO CRD42023430557. Methods: A systematic review and meta-analysis of five databases was performed between June 2023- July 2023. Key outcomes extracted included patient demographics, overall survival (OS), progression-free survival (PFS) and objective response rates (ORR). ORR was calculated using a random effects model and inverse variance methods. Time-to-event outcomes including PFS and OS, were extracted digitally from available Kaplan- Meier curves using the IPDfromKM tool and individual patient data (IPD) was generated as per Guyot et al. The PFS and OS data from individual studies were then pooled using a multivariate extension of the DerSimonian–Laird method to generate summary survival curves. Results: The final 23 trials (5 Phase 1b, 16 Phase II and 3 Phase 3) encompassed 880 patients were retrieved. Pooled ORR was 9.0% overall (2.9% for targeted therapy, 12.3% for chemotherapy and 15.3% for immunotherapy). Median OS was 9.9 months (7.4 months for targeted therapy, 11.2 months for chemotherapy and 10.6 months for immunotherapy). Median PFS was 2.6 months (2.7 months for targeted therapy, 3.0 months for chemotherapy and 2.1 months for immunotherapy). Kaplan-Meier curves for OS were available for 10 treatment lines (n = 605), with a pooled median OS of 9.9 months (95% CI 7.7-11.9) and 12-month OS of 41.6% (95CI 33.1-51.2). Median OS was 7.4 months for patients receiving targeted therapy (95% CI 4.7–12.0), 11.2 months for patients receiving chemotherapy (95% CI 6.9–14.7) and 10.6 months for patients receiving immunotherapy (95% CI 4.4–13.2]. 12-month OS was 30.4% (95% CI 15.9-58.3) for patients receiving targeted therapy, 45.4% (95% CI 33.7-61.2) for patients receiving chemotherapy and 45.3% (95% CI 36.2-56.6) for patients receiving immunotherapy. Conclusions: This study found that current treatments strategies confer limited survival and response benefit in mACC and highlight the need for research into the pathogenesis and novel strategies in the disease. Immunotherapy and chemotherapy demonstrate modest benefits for patients and future trials should attempt to surpass the survival benchmarks set in this study.

Lenvatinib Versus Atezolizumab Plus Bevacizumab in the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis of Real-World Studies.

Immunotherapy has revolutionized the treatment of hepatocellular carcinoma (HCC). However, whether adding immunotherapy to antiangiogenic therapy benefits patients with unresectable HCC (uHCC) more in the first-line setting remains controversial. In this analysis, we compared the clinical outcomes of lenvatinib monotherapy with atezolizumab plus bevacizumab combination therapy in advanced uHCC in real-world clinical practice. The MEDLINE, Embase, and Cochrane CENTRAL databases were systematically searched on 23 April 2023. The "metaSurvival" and "meta" packages of the R software (version 4.2.2) were used to summarize the survival curves and meta-analyze the survival data. Overall survival (OS) and progression-free survival (PFS) were defined as dual primary endpoints. Secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). Overall, the pooled median OS was 18.4 months in the lenvatinib group versus 18.5 months in the atezolizumab plus bevacizumab group; the pooled median PFS was 6.9 months in the lenvatinib group versus 7.3 months in the atezolizumab plus bevacizumab group. Lenvatinib therapy showed similar OS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.55-1.52, p = 0.72] and PFS (HR: 0.79, 95% CI: 0.56-1.12, p = 0.19) compared with atezolizumab plus bevacizumab therapy. In addition, a comparable ORR [odds ratio (OR): 0.89, 95% CI: 0.65-1.20, p = 0.44) was observed between lenvatinib and atezolizumab plus bevacizumab. Comprehensive analysis suggested that lenvatinib monotherapy exhibited survival outcomes comparable to those of atezolizumab plus bevacizumab combination therapy, which may provide useful insights for clinicians in future clinical practice.

Tumor Treating Fields (TTFields) for Newly Diagnosed Glioblastoma in the Real World: A Systematic Review and Survival Meta-Analysis

Tumor Treating Fields (TTFields) are electric fields that exert forces on cancer cells, disrupting processes critical for cancer cell viability and tumor progression. TTFields therapy is FDA-approved for patients with newly diagnosed glioblastoma (GBM) on the basis of the randomized controlled EF-14 study (NCT00916409). Subsequent approvals and increased worldwide adoption of TTFields has led to the question of whether or not a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role. PubMed, Embase, and the Cochrane Library were searched using pre-defined terms, to identify clinical studies (including comparative and single-cohort studies) evaluating overall survival (OS) in adult patients with GBM treated with TTFields therapy added to radiochemotherapy. The Cochran Q test was used to assess inter-study heterogeneity, and results were quantified using the Higgins I2 statistic. Data were pooled, and a survival curve created using a distribution-free random-effects method. Records identified from the literature search were screened and distilled using pre-specified methods, down to 8 studies evaluating the clinical efficacy of TTFields therapy in newly diagnosed GBM (spanning diverse geographic regions). Six studies (reporting on a total of 1378 patients) compared the addition of TTFields therapy to standard of care (SOC) vs SOC alone, and were included in a pooled analysis for OS. Meta-analysis of data from the 6 studies indicated a significant OS benefit for patients receiving TTFields therapy vs those who did not (hazard ratio [HR]: 0.62; 95% CI, 0.52-0.73; P < 0.001). Sensitivity analysis confirmed the pooled effect was robust and not dependent on any individual study. Of the 6 included in the analysis, 5 were post-approval for which the pooled median OS was 22.2 months (95% CI, 17.3-42.6) vs 17.3 months (95% CI, 13.6-22.0) for the TTFields/SOC group and the SOC group, respectively. Rates of gross total resection were numerically higher in the real-world setting, irrespective of TTFields use. Among studies reporting data on TTFields device usage, an average device usage rate of 75% or higher was found to consistently correlate with prolonged OS when compared to an average usage rate < 75% (pooled HR: 0.63; 95% CI, 0.48-0.83; P = 0.001). Meta-analysis of comparative studies suggests a significant OS benefit when TTFields therapy is added to standard radiochemotherapy for patients with newly diagnosed GBM, and that a ≥ 75% usage rate may translate to clinical benefit in the real-world setting.

Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients.

Guidelines recommend that hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and/or hepatic vein tumor thrombosis (HVTT) should undergo systemic therapy. However, recent data suggest that surgical resection may be beneficial in selected cases, but outcomes are heterogenous. We aimed to estimate pooled overall survival (OS), recurrence free survival (RFS) and complication rates in HCC patients with macrovascular invasion (MVI) following surgical resection. In this systematic review and meta-analysis, two investigators independently searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020, without language restrictions, for studies reporting outcomes of adult HCC patients with MVI who underwent liver resection with curative intent. We screened 8,598 articles and included 40 studies involving 8,218 patients. Among all patients with MVI, the pooled median OS was 14.39 months [95% confidence interval (CI): 10.99-18.84], 1-year OS was 54.47% (95% CI: 46.12-62.58%) and 3-year OS was 23.20% (95% CI: 16.61-31.42%). Overall, 1- and 3-year RFS were 27.70% (95% CI: 21.00-35.57%) and 10.06% (95% CI: 6.62-15.01%), respectively. Among patients with PVTT, median OS was 20.41 months in those with segmental/2nd order involvement compared to 12.91 months if 1st order branch was involved and 6.41 months if the main trunk was involved. The pooled rate of major complications was 6.17% (95% CI: 3.53-10.56%). Overall median survival was 14.39 months for HCC patients with MVI following resection. Median survival was higher in PVTT with segmental/2nd order involvement at 20.41 versus 6.41 months if the main trunk was involved.

Efficacy and Safety of PD-1/PD-L1 Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

Programmed cell death1 (PD-1) and programmed cell death ligand1 (PD-L1) inhibitors have been increasingly employed for the treatment of various cancers in clinical practice. This study aimed to systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitors for advanced hepatocellular carcinoma (HCC). PubMed, EMBASE, Cochrane library, Web of Science, and Abstracts of American Society of Clinical Oncology proceedings databases were searched. Objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), median overall survival (OS), and incidence of adverse events (AEs) and drug withdrawal were pooled. Odds ratio (OR) and hazard ratio (HR) were calculated to analyze the difference in the ORR, DCR, PFS, and OS between groups. Among the 14,902 initially identified papers, 98 studies regarding use of PD-1/PD-L1 inhibitors in advanced HCC were included. Based on different criteria of response in solid tumors, the pooled ORR, DCR, and median PFS was 16-36%, 54-74%, and 4.5-6.8months, respectively. The pooled median OS was 11.9months. Compared to multitarget tyrosine kinase inhibitors (TKIs), PD-1/PD-L1 inhibitors monotherapy significantly increased ORR (OR 2.73, P < 0.00001) and OS (HR 0.97, P = 0.05), and PD-1/PD-L1 inhibitors combined with TKIs significantly increased ORR (OR 3.17, P < 0.00001), DCR (OR 2.44, P < 0.00001), PFS (HR 0.58, P < 0.00001), and OS (HR 0.58, P < 0.00001). The pooled incidence of all-grade AEs, grade ≥ 3 AEs, and drug withdrawal was 71%, 25%, and 7%, respectively. On the basis of the present systematic review and meta-analysis, PD-1/PD-L1 inhibitors should be the preferred treatment choice for advanced HCC owing to their higher antitumor effect and improved outcomes.

Survival times of patients with glioblastoma in low- and middle-income countries: a systematic review and meta-analysis.

Little is known about the survivorship of glioblastoma (GBM) patients in low- and middle-income countries (LMICs). We hypothesize that this would be lower than published figures for high-income countries due to cancer health disparities. We performed a systematic review and meta-analysis to estimate the median overall survival (OS) of GBM in LMICs and determine factors affecting OS. A systematic review of 12 electronic databases was conducted according to PRISMA guidelines to identify studies of newly diagnosed adult GBM patients done in countries classified as LMIC by the World Bank (WB) from inception to December 2020. Random effects meta-analysis of collected median overall survival data was done. Subgroup analysis and meta-regression were done to determine if WB income classification (WBIC), start year of recruitment (pre- or post-popularization of the standard Stupp protocol), and treatment modality affected OS. The 24 articles (n = 2,552) that met the inclusion criteria were from 8 low-middle income and upper-middle income countries, with 0 articles from low-income countries. Random effects analysis of 24 studies showed a pooled median OS of 14.17 months (95% CI 12.90-15.43, I2 = 79). Subgroup analysis showed a significant difference (p < 0.05) in the pooled median OS of studies predating Stupp protocol (12.54 mo, 95% CI 11.13-13.96, I2 = 80%; n = 1027) and studies postdating Stupp protocol (15.64 mo, 95% CI 13.58-17.69, I2 = 77; n = 1412). Subgroup analysis of WBIC and treatment modalities did not show significant differences. Published data on the survivorship of GBM patients in LMICs is sparse, highlighting the need for good quality pragmatic studies from LMICs. The limited evidence suggests improving survivorship after introduction of the Stupp protocol.

P774: CLINICAL OUTCOMES ASSOCIATED WITH AZACITIDINE MONOTHERAPY FOR TREATMENT-NAIVE PATIENTS WITH HIGHER-RISK MYELODYSPLASTIC SYNDROME (HR MDS): A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS

Background: Azacitidine (AZA) is a standard of care for patients with HR MDS; however, the number of large data sets describing outcomes of AZA monotherapy in HR MDS is limited. Aims: To aggregate clinical outcomes data associated with AZA monotherapy for treatment-naive patients with HR MDS. Methods: CENTRAL, EMBASE, and MEDLINE were searched to identify interventional, prospective, and retrospective observational studies using AZA monotherapy in treatment-naive HR MDS (defined as intermediate-2 or high risk by International Prognostic Scoring System [IPSS] or intermediate to very high risk by Revised IPSS). Inclusion of observational studies was limited to those with >20 patients in the AZA monotherapy arm. Responses according to International Working Group (IWG) 2000 or IWG 2006 criteria—including complete remission (CR) rate, overall response rate (ORR; defined as CR, marrow CR [mCR], partial remission, and hematologic improvement), overall survival (OS), duration of response (DOR), and time to response (TTR)—were extracted. All articles were reviewed by 2 independent abstractors. Response rates were synthesized using random-effects models; median of medians was used for OS, DOR, and TTR. Results: Of 3250 abstracts identified, 34 publications describing 16 studies met inclusion criteria: 5 randomized controlled trials (RCTs), 3 prospective studies, and 8 retrospective studies. None of the response endpoints were reported in all studies (Table). The pooled CR rates, reported in 2 RCTs (N=55), 1 prospective study (N=27), and 3 retrospective studies (N=509), were 14%, 11%, and 16%, respectively. The pooled CR rate across all studies (N=591) was 16% (95% CI, 13%-19%). The mCR rate from 1 RCT was 19% (95% CI, 10%-34%; N=42), and the pooled mCR rate from 2 retrospective studies was 18% (95% CI, 13%-26%; N=126). The pooled ORRs ranged from 44% to 55% across RCTs, prospective studies, and retrospective studies. The pooled median OS was 16.7 months in 3 RCTs (N=161), 16.5 months in a single prospective study (N=34), and 14.4 months in 5 retrospective studies (N=1472). The pooled median OS across all studies (N=1667) was 16.4 months (95% CI, 12.0-17.3 months). The pooled median DOR was 10.1 months (95% CI, 9.1-11.0 months), and the median TTR was 4.6 months (95% CI, 3.0-9.0 months). Table: - Outcomes in treatment-naive patients with HR MDS treated with AZA monotherapy Endpoint RCTs Total N Outcome(95% CI) Prospectivestudies Total N Outcome(95% CI) Retrospective studies Total N Outcome(95% CI) All studies Total N Outcome(95% CI) CR rate, % 2 55 14(6-31) 1 27 11(4-29) 3 509 16(13-20) 6 591 16(13-19) mCR rate, % 1 42 19(10-34) 0 - - 2 126 18(13-26) 3 168 19(13-25) ORR, % 3 159 50(42-57) 1 27 44(27-63) 4 967 55(42-67) 8 1153 52(44-60) Median OS, months 3 161 16.7(9.5-26.3) 1 34 16.5(10.4-21.9) 5 1472 14.4(11.6-17.3) 9 1667 16.4(12.0-17.3) Median DOR, months 1 20 9.1(6.0-NR) 0 - - 1 405 11.0 (NA) 2 425 10.1(9.1-11.0) Median TTR, months 1 42 4.6(2.0-6.5) 0 - - 2 493 6.0 (3.0-9.0) 3 535 4.6(3.0-9.0) NA, not available; NR, not reached. Summary/Conclusion: These findings provide evidence that benefit with AZA monotherapy in treatment-naïve patients with HR MDS is limited. Opportunity exists for novel therapies to increase CR rates and prolong survival.

Platinum-doublet chemotherapy for advanced gastroenteropancreatic neuroendocrine carcinoma: A systematic review and meta-analysis.

e16217 Background: Neuroendocrine carcinoma (NEC) is a poorly differentiated pathological neuroendocrine neoplasm exhibiting aggressive clinical behaviors; the most common extrapulmonary site is the gastroenteropancreatic (GEP) system. Treatment strategies for GEP-NEC are primarily based on those employed for small cell lung cancer, and platinum-doublet chemotherapy, such as platinum plus etoposide (EP) or platinum plus irinotecan (IP), has been widely used as initial systemic therapy for patients with advanced/metastatic disease; however, clinical data for GEP-NEC are chiefly derived from small-scale retrospective studies, and the reported efficacy is heterogenous among studies. Methods: We conducted a systematic database search using PubMed/MEDLINE and EMBASE. Eligible studies included randomized trials, single-arm trials, prospective observational studies, and retrospective studies documenting the clinical efficacy of platinum-doublet chemotherapy (EP and IP) for advanced GEP-NEC. The pooled overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were calculated and weighted using generic inverse variance in a random-effects meta-analysis model. Results: Based on initial screening and eligibility assessment, 19 studies with a combined total of 1,157 patients were identified through a systematic review. Studies included 3 comparative studies between EP and IP with 1 randomized phase II trial and 2 retrospective studies. The pooled ORR in all patients who received the platinum-doublet regimen was 49.1% (95% confidence interval [CI], 41.8–56.5), and subgroup analysis for EP and IP groups showed ORRs of 44.4% (95% CI, 35.9–53.0) and 59.4% (95% CI, 48.0–70.8), respectively. According to the three studies directly comparing EP to IP, the odds ratio of ORR using EP as reference was 1.95 (95% CI, 0.86–4.39, P = 0.11). The pooled median OS in all patients who received the platinum-doublet regimen was 12.9 (95% CI, 10.9–15.3) months, where EP and IP subgroups had median OS of 12.9 (95% CI, 10.8–15.4) and 12.9 (95% CI, 6.0–27.8) months, respectively. The pooled median PFS was 5.4 (95% CI, 4.5–6.4) months in all patients with platinum-regimen, 5.4 (95% CI, 4.5–6.5) months in the EP subgroup, and 4.0 (95% CI, 1.4–11.7) months in IP subgroup, respectively. Conclusions: This study was the first systematic review and meta-analysis assessing patients with GEP-NEC; it has revealed considerable ORR following platinum-doublet chemotherapy. EP and IP regimens can be reasonably employed in patients with advanced GEP-NEC. These results can serve as reference information for clinicians in deciding a suitable chemotherapy regimen. Larger randomized trials and individual patient data meta-analyses are warranted to obtain robust clinical evidence.

Platinum-doublet chemotherapy for advanced gastroenteropancreatic neuroendocrine carcinoma: a systematic review and meta-analysis

BackgroundPlatinum-doublet chemotherapy has been conventionally used for patients with advanced gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) but evidence of chemotherapy is based on studies with small sample sizes and remains scarce. Thus, we conducted a systematic review and meta-analysis to elucidate the efficacy of platinum-doublet chemotherapy for advanced GEP-NEC.MethodsWe performed a database search in PubMed/MEDLINE and EMBASE. Eligible studies were prospective and retrospective studies documenting the efficacy of platinum plus etoposide (EP) and platinum plus irinotecan (IP) for advanced GEP-NEC. Overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were pooled and weighted using generic inverse variance in a random-effects meta-analysis model.ResultsNineteen studies including 1157 patients were identified. The ORR of the platinum-doublet regimen, EP, and IP was 49.1% (95% confidence interval [CI], 41.8–56.5), 44.4% (95% CI: 35.9–53.0), and 59.4% (95% CI: 48.0–70.8). The pooled median OS of the platinum-doublet regimen, EP, and IP was 12.9 months (95% CI:10.9–15.3), 12.9 months (95% CI: 10.8–15.4), and 12.9 months (95% CI: 6.0–27.8), and the pooled median PFS of the platinum-doublet regimen, EP, and IP was 5.4 months (95% CI: 4.5–6.4), 5.4 months (95% CI 4.5–6.5), and 4.0 months (95% CI: 1.4–11.7), respectively.ConclusionConsiderable response rate and survival time of the platinum-doublet regimen for advanced GEP-NEC were observed. IP and EP regimens can be reasonably applicable and these results provide a reference for oncologists in deciding the suitable regimen for patients with advanced GEP-NEC.

Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma: A Systemic Review and Meta-Analysis.

BackgroundChimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory hematological malignancies. However, its efficacy in glioblastoma remains unclear. Here, we performed a systematic review to summarize the safety and efficacy of CAR T-cell therapy in glioblastoma.MethodsThe PubMed, EMBASE, and Cochrane databases were searched to identify articles published before June 30, 2021 describing the use of CAR T-cell therapy in glioblastoma. Information on the toxicity of CAR T-cell therapy was summarized. The pooled objective response rate (ORR) and overall survival (OS) of patients who underwent CAR T-cell therapy were estimated using a random-effects model with an inverse-variance weighting model and quantile estimation method, respectively.ResultsOf 397 articles identified, eight studies including 63 patients with recurrent glioblastoma treated with various CAR T-cell regimens were included in the analysis. Six (9.5%) patients developed cytokine release syndrome (grade ≤2), and 16 (25.4%) experienced non-critical neurological events. The pooled ORR was 5.1% (95% confidence interval [CI], 0.0–10.4; I2 = 0.05%), and the pooled median OS was 8.1 months (95% CI, 6.7–9.5; I2 = 0.00%).ConclusionAlthough CAR T-cell therapy is a relatively safe therapeutic option in patients with glioblastoma, it shows marginal efficacy, suggesting that further research is necessary for its translation into clinical practice for the treatment of recurrent glioblastoma.

Efficacy and security of tumor vaccines for hepatocellular carcinoma: a systemic review and meta-analysis of the last 2 decades.

Tumor vaccines for hepatocellular carcinoma (HCC) is an area of intense interest. Tremendous clinical trials have been conducted globally, but the efficacy and security of tumor vaccines are elusive. The aim of our study was to evaluate the efficacy and security of tumor vaccines. All relevant studies were identified in PubMed, EMBASE, Web of science and Cochrane Library databases. Objective response rate (ORR), median overall survival (OS), or median progression-free survival (PFS) and 95% CI were meta-analyzed based on the random-effects model. The individual-level data of OS, PFS were pooled by conducting survival analysis. All observed adverse events were collected. 31 studies containing 35 eligible cohorts with 932 HCC patients were included. The pooled ORR were 7% (95% CI 3-14%), while ORR of dendritic cell (DC) vaccine (19%, 95% CI 11-29%) were highly significant than ORR of peptide vaccine (1%, 95% CI 0-5%). The pooled median OS and PFS were 13.67months (95% CI 8.20-22.80) and 6.19months (95% CI 2.97-12.91), respectively. The pooled median OS (DC vaccine: median OS = 21.77months, 95% CI 18.33-25.86; Peptide vaccine: median OS = 10.08months, 95% CI 5.23-19.44) and PFS (DC vaccine: median PFS = 11.01months, 95% CI 5.25-23.09; Peptide vaccine: median PFS = 1.97months, 95% CI 1.53-2.54) of DC vaccine were also longer than that of peptide vaccine. HBV-related HCC may acquire more benefits from tumor vaccines than HCV-related HCC. In almost all studies, the observed toxicities were moderate even tiny. Tumor vaccines for HCC, especially DC vaccine, are safe and worth exploring. More high-quality prospective studies are warranted.

Effectiveness and safety of combined therapy versus monotherapy based on immune checkpoint inhibitors and/or targeted drugs as salvage treatment for advanced urothelial carcinoma: a systematic review and meta-analysis.

BackgroundThe standard salvage regimen for the patients with advanced urothelial carcinoma (UC) is uncertain, although lots of novel agents are recommended, including immune checkpoint inhibitors (ICIs) and targeted drugs (TDs). We aimed to compare the effectiveness and safety of combined therapy of novel agents (CNA) and monotherapy of novel agents (MNA) as salvage therapy for advanced UC.MethodsStudies exploring CNA and/or MNA for advanced UC in second-line setting were searched from PubMed, Embase, Cochrane Library, and Web of Science. The data of objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), median overall survival (OS), and grade 3-4 adverse effects rate (grade 3-4 AEs%) were pooled for analyses. Cochrane risk of bias tool was applied for the quality judgment of randomized controlled studies (RCTs).ResultsForty-one arms from 37 studies including 4,691 patients were included. Significant differences were presented in pooled ORR (22.9% versus 12.2%, OR =1.88, P<0.001) and DCR (62.7% versus 37.5%, OR =2.53, P<0.001) between CNA and MNA groups. The pooled median PFS was 3.66 months in CNA group versus 2.16 months in MNA group (WMD =1.50, P=0.028). No significant difference in pooled median OS was found between two groups (7.93 versus 7.50 months, WMD =0.43, P=0.449). 63.7% versus 25.4% of pooled grade 3-4 AEs% could be seen in CNA and MNA groups (OR =3.52, P<0.001). Additionally, the pooled results of PFS-6m and OS-6m in CNA group demonstrated significant advantages over MNA group (31.5% versus 28.7%, OR =1.31, P=0.049; 66.0% versus 56.7%, OR =1.34, P=0.029, respectively). In the subgroup analysis of CNA, use of ICIs, the positive expression of PD-L1 and ECOG-PS =0 were significantly associated with superior clinical outcomes (P<0.05).DiscussionFor advanced UC patients after first line agents, CNA had potential benefits than MNA in terms of ORR, DCR, median PFS, PFS-6m and OS-6m. However, CNA was associated with a significantly higher grade 3-4 AEs%. Furthermore, potential advantages were presented in CNA patients with ICIs usage, positive PD-L1 expression and ECOG-PS =0.

Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in extensive disease small cell lung cancer.

The aim of this study is to assess how clinical outcomes in real-world (effectiveness) correspond to the outcomes in clinical trials (efficacy) of systemic treatments for extensive disease small cell lung cancer (ED SCLC). All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. For every patient, an efficacy-effectiveness factor (EE factor) was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment. From 792 diagnosed patients, 568 (72%) started with first-line treatment. Overall, the median EE factor was 0.79 (P < .001 from 1.00). Poor performance status (ECOG≥2) and a higher age at diagnosis (age ≥ 65 years) were independent predictors for a lower EE factor. The EE gap was 43% in patients with both age ≥ 65 years and ECOG ≥2 (EE factor 0.57). The mean age and the proportion of patients with ECOG≥2 in real-world were different from those in clinical trials (mean age of 66 versus 62 years, and ECOG≥2 25% versus 17%; both P < .001). OS of patients with ED SCLC treated with systemic therapy in real-world practice is 21% shorter than for patients included in trials. Age at diagnosis and performance status partly explain this gap.

Surgery versus external beam radiotherapy for hepatocellular carcinoma involving the inferior vena cava or right atrium: A systematic review and meta-analysis.

We investigated the efficacy and safety of surgery and external beam radiotherapy (EBRT), in patients with hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) through a comparative meta-analysis. A systematic search of PubMed, MEDLINE, EMBASE, and the Cochrane library was performed for entries until July 2020. Eighteen studies with 22 cohorts were included, encompassing 755 patients. The pooled median overall survival (OS) and 1- and 2-year OS rates were 14.2months, 55.6%, and 27.4%, respectively. The pooled median OS in the surgery and EBRT arms were 15.3 and 11.7months, respectively. The pooled 1-year OS rate in the surgery arm was significantly higher than that in the EBRT arm (62.4%, 95% CI: 53.8%-70.3% vs 48.8%, 95% CI: 40.9-56.8, respectively; P=.023), while the 2-year OS rates were similar (27.5%, 95% CI: 19.7%-37.1% vs 26.9%, 95% CI: 20.7-34.2, respectively; P=.913). In the surgical arm, the perioperative mortality and grade ≥3 complication rates were 0%-7.6% and 3.9%-67%, respectively. Grade ≥3 complications and radiation-induced liver disease were rarely observed in the EBRT arm. Surgery could be an effective local modality for achieving the best survival rate, though it requires efforts to minimize morbidities and careful patient selection. EBRT, as a noninvasive modality, is a valid palliative option, especially for high-risk patients with a shorter life expectancy.

Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in metastatic nonsmall cell lung cancer.

The divergence between clinical trial results and real-world outcomes is largely unknown for many cancer types. The present study aims overall to assess the efficacy–effectiveness gap (difference between outcomes in clinical trials and the real world) in systemic treatment for metastatic nonsmall cell lung cancer (NSCLC).All patients diagnosed with stage IV NSCLC between 2008 and 2014 within a network of seven Dutch large teaching hospitals (Santeon) were studied. For every patient, an efficacy–effectiveness (EE) factor was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment.From 2989 diagnosed patients, 1214 (41%) started with first-line treatment. For all studied regimens, real-world OS was shorter than OS reported in clinical trials. Overall, the EE factor was 0.77 (95% CI 0.70–0.85; p<0.001). Real-world patients completed their treatment plan less often and proceeded less frequently to further lines of treatment. These parameters together with Eastern Cooperative Oncology Group performance status explained 35% of the variation in EE factor.Survival of patients with metastatic NSCLC treated with chemotherapy or targeted therapy in real-world practice is nearly one-quarter shorter than for patients included in trials. Patients' performance status, earlier discontinuation and fewer subsequent lines of treatment partly explained this difference.

Efficacy and safety of apatinib in patients with advanced nonsmall cell lung cancer that failed prior chemotherapy or EGFR-TKIs: A pooled analysis.

Background:Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor-2. A weighted pooled analysis was performed to evaluate the clinical outcome, efficacy, and toxicity of apatinib in patients with advanced nonsmall cell lung cancer (NSCLC) that failed prior treatment with chemotherapy or epidermal growth factor receptor-TKIs (EGFR-TKIs).Methods:The literature published in PubMed, Embase, and Cochrane Library databases was searched (from inception to November 30, 2017) for eligible trials using the following search terms: apatinib AND (lung cancer OR NSCLC). Meeting abstracts were also reviewed to identify appropriate studies. Inclusion criteria were as follows: prospective or retrospective studies that evaluated efficacy and/or safety of apatinib in patients with advanced NSCLC that failed prior chemotherapy or EGFR-TKIs; primary outcome included one of these endpoints, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), or adverse events (AEs); English language; and number of cases in the study ≥10 cases.Results:A total of 457 patients with advanced NSCLC were treated with apatinib in 14 studies (10 retrospective and 4 prospective studies) and were included in this pooled analysis. The pooled median PFS was 4.77 months [95% confidence interval (CI), 4.11–5.00] in all groups, 4.80 months (95% CI, 4.65–4.95) in the 750 mg apatinib (high-dose) group, and 3.88 months (95% CI, 3.11–4.65) in the 250 to 500 mg apatinib (low-dose) group. Median PFS stratified by single apatinib therapy or apatinib combined with continuous EGFR-TKIs was 4.76 months (95% CI, 3.66–5.06) and 5.20 months (95% CI, 3.66–6.74), respectively. The pooled median OS, ORR, and DCR values were 6.85 months, 18%, and 72%, respectively; pooled median ORR and DCR were 15% and 72% in the 750 mg apatinib group versus 20% and 72% in the 250 to 500 mg apatinib group. ORR and DCR stratified by therapeutic regimens were 14% and 70% for single-agent apatinib, 29% and 88% for apatinib combined with continuous EGFR-TKIs, and 26% and 63% for apatinib combined with chemotherapy, respectively. The pooled AE rates of grade 3/4 were hypertension (7%), proteinuria (3%), hand-foot-skin reaction (6%), fatigue (4%), decreased appetite (1.1%), oral mucositis (3%), and thrombocytopenia (3%).Conclusion:Apatinib has promising antitumor activity and manageable toxicity profile in patients with advanced NSCLC that failed prior chemotherapy or EGFR-TKIs. This result needs to be confirmed through the ongoing Phase III clinical trial.

A randomized phase II study of axitinib (AG-013736) and gemcitabine versus gemcitabine in advanced pancreatic cancer, preceded by a phase I component

4551 Background: The current standard of care for patients (pts) with advanced pancreatic cancer (APC) is gemcitabine (GEM)- based chemotherapy. Axitinib (AG) is a potent inhibitor of vascular endothelial growth factor receptors. A phase I study of AG in solid tumors identified 5 mg BID as the therapeutic starting dose. The main objectives of this trial are to determine whether the overall survival (OS) of the combination of AG and GEM is superior to that of GEM alone as first-line therapy in pts with APC, and to determine doses of AG and GEM that can be safely administered together. Methods: 8 pts were treated on the phase 1 (P1) portion of this trial. For the phase 2 (P2) portion of the trial, 103 pts with locally advanced or metastatic disease, no prior GEM or VEGF/VEGFR inhibitors, PS 0–2 were randomized (2:1) to GEM 1,000 mg/m2 over 30 minutes on days (D) 1, 8, 15 every 28 D with or without AG at a starting dose of 5 mg po BID between Jan 06 and Aug 06. CT scans were performed every 2 cycles. Results: Data from the evaluable P1 pts (n=5) indicated that PK of GEM and AG appeared to be unchanged in combination. The GEM mean plasma exposure (AUC) was 11,348 alone vs 12,840 ng.h/mL with AG; similarly mean steady-state AG AUC was 250 alone vs 270 ng.h/mL with GEM. 3 of 8 pts had a PR. The median number of days on study drug was 158 days (range: 57–330 days) with 2 pts ongoing. Data from the randomized P2 pts: male 48%; median age 62 (36- 81); PS 0/1 vs 2: 91% vs 9%; 41% with locally advanced disease; 59% with metastatic disease. The most commonly reported adverse events are anemia (48%), alk phos elevations (48%), leukopenia (45%), neutropenia (42%), LFT elevations (39%), and thrombocytopenia (27%). The most common non-hematologic adverse events are nausea (24%), vomiting (20%), fatigue (19%), diarrhea (18%), anorexia (18%), constipation (13%), dyspnea (12%), and pyrexia (12%). 55 events have been reported in the 103 P2 pts. The pooled median OS is 203 days with a 95% CI of (158, not estimable). The median follow-up time is currently 223 days. Conclusions: AG can be safely administered at a starting dose of 5 mg BID in combination with standard dose GEM in patients with APC. Final safety and OS results by treatment arm will be presented. [Table: see text]