scholarly journals Meta-analysis of efficacy and adverse events of erlotinib-based targeted therapies for advanced/metastatic non-small cell lung cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (49) ◽  
pp. 86816-86827 ◽  
Author(s):  
Fei Li ◽  
Shu-Hua Zhang ◽  
Li-Min Pang
2019 ◽  
Vol 19 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Bing-Di Yan ◽  
Xiao-Feng Cong ◽  
Sha-Sha Zhao ◽  
Meng Ren ◽  
Zi-Ling Liu ◽  
...  

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). </P><P> Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. </P><P> Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). </P><P> Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii204-ii204
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Behnam Sadeghirad ◽  
Jiawen Deng ◽  
Winston Hou ◽  
...  

Abstract BACKGROUND Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including &gt; 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach. RESULTS Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25-554). All trials included adult patients with histologically proven NSCLC and &gt;1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3-799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3-254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7-289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5-167.5). CONCLUSIONS Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.


2020 ◽  
Vol 9 (4) ◽  
pp. 1063 ◽  
Author(s):  
Tung Hoang ◽  
Seung-Kwon Myung ◽  
Thu Thi Pham ◽  
Jeongseon Kim ◽  
Woong Ju

This study aims to investigate the efficacy of targeted therapies in the treatment of non-small cell lung cancer (NSCLC) by using a network meta-analysis of clinical trials. PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov were searched by using keywords related to the topic on 19 September 2018. Two investigators independently selected relevant trials by pre-determined criteria. A pooled response ratio (RR) for overall response rate (ORR) and a hazard ratio (HR) for progression-free survival (PFS) were calculated based on both the Bayesian and frequentist approaches. A total of 128 clinical trials with 39,501 participants were included in the final analysis of 14 therapeutic groups. Compared with chemotherapy, both ORR and PFS were significantly improved for afatinib, alectinib, and crizotinib, while only PFS was significantly improved for cabozantinib, ceritinib, gefitinib, and osimertinib. Consistency was observed between the direct and indirect comparisons based on the Bayesian approach statistically and the frequentist approach visually. Cabozantinib and alectinib showed the highest probability for the first-line treatment ranking in ORR (62.5%) and PFS (87.5%), respectively. The current network meta-analysis showed the comprehensive evidence-based comparative efficacy of different types of targeted therapies, which would help clinicians use targeted therapies in clinical practice.


Author(s):  
Calvin S.H. Ng ◽  
John K. MacDonald ◽  
Sebastien Gilbert ◽  
Ali Z. Khan ◽  
Young T. Kim ◽  
...  

Objective Video-assisted thoracic surgery (VATS) lobectomy was introduced over 25 years ago. More recently, the technique has been modified from a multiport video-assisted thoracic surgery (mVATS) to uniportal (uVATS) and robotic (rVATS), with proponents for each approach. Additionally most lobectomies are still performed using an open approach. We sought to provide evidence-based recommendations to help define the optimal surgical approach to lobectomy for early stage non-small cell lung cancer. Methods Systematic review and meta-analysis of articles searched without limits from January 2000 to January 2018 comparing open, mVATS, uVATS, and rVATS using sources Medline, Embase, and Cochrane Library were considered for inclusion. Articles were individually scrutinized by ISMICS consensus conference members, and evidence-based statements were created and consensus processes were used to determine the ensuing recommendations. The ACC/AHA Clinical Practice Guideline Recommendation Classification system was used to assess the overall quality of evidence and the strength of recommendations. Results and recommendations One hundred and forty-five studies met the predefined inclusion criteria and were included in the meta-analysis. Comparisons were analyzed between VATS and open, and between different VATS approaches looking at oncological outcomes (survival, recurrence, lymph node evaluation), safety (adverse events), function (pain, quality of life, pulmonary function), and cost-effectiveness. Fifteen statements addressing these areas achieved consensus. The highest level of evidence suggested that mVATS is preferable to open lobectomy with lower adverse events (36% versus 42%; 88,460 patients) and less pain (IIa recommendation). Our meta-analysis suggested that overall survival was better (IIb) with mVATS compared with open (71.5% versus 66.7% 5-years; 16,200 patients). Different VATS approaches were similar for most outcomes, although uVATS may be associated with less pain and analgesic requirements (IIb). Conclusions This meta-analysis supports the role of VATS lobectomy for non-small cell lung cancer. Apart from potentially less pain and analgesic requirement with uVATS, different minimally invasive surgical approaches appear to have similar outcomes.


2019 ◽  
Author(s):  
Hye Duck Choi ◽  
Min Jung Chang

Abstract Background: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors used to treat EGFR mutation positive non-small-cell lung cancer (NSCLC). Skin rash and diarrhea are well-known and common adverse events in patients receiving erlotinib, whereas other adverse events, including eye, liver, or renal disorders have not been evaluated adequately. This meta-analysis aimed to evaluate the ocular, hepatobiliary, and renal toxicities of erlotinib in patients with NSCLC cancers. Methods: In total, sixty studies were assessed, and the results of the included studies were quantitatively integrated using meta-analysis. The incidence of ocular, hepatobiliary (alanine aminotransferase [ALT] and bilirubin elevations; other hepatic adverse events), and renal adverse events were estimated. Additionally, the erlotinib-treated groups and the control groups (placebo or other treatment) were compared with respect to ocular disorders and ALT elevation. The study protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO) CRD42018093758. Results: The overall incidence of ocular disorders was 3.30% (95% confidence interval [CI] 2.20%–5.00%). The incidence of ALT elevation, bilirubin elevation, and other hepatobiliary disorders was 6.40% (95% CI 3.90%–10.4%), 3.80% (95% CI 2.30%–6.10%), and 1.00% (95% 0.60%–1.80%), respectively. The incidence of renal disorder was 3.10% (95% CI 1.90%–5.00%). The risk of ocular toxicity in the erlotinib treatment group was significantly increased (risk ratio = 2.91; 95% CI 1.70–4.98) compared to that in the control group. ALT elevation was not significantly different between the two groups. Conclusion: Based on the results, careful monitoring of ocular toxicity in patients receiving erlotinib should be recommended and closer monitoring of hepatic toxicity should be also recommended in patients with liver-related risk factors.


2011 ◽  
Vol 67 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Peng Chen ◽  
Long Wang ◽  
Bing Liu ◽  
Hai-Zhong Zhang ◽  
Hong-Chen Liu ◽  
...  

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii12-ii13
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Behnam Sadeghirad ◽  
Jiawen Deng ◽  
Winston Hou ◽  
...  

Abstract BACKGROUND Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including &gt; 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach. RESULTS Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25–554). All trials included adult patients with histologically proven NSCLC and &gt;1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3–799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3–254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7–289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5–167.5). CONCLUSIONS Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.


2022 ◽  
Vol 102 ◽  
pp. 108353
Author(s):  
Chunyang Zhou ◽  
Minghao Li ◽  
Zijian Wang ◽  
Dianzheng An ◽  
Baosheng Li

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