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Bayesian network meta-analysis of efficacy and safety of neoadjuvant therapy for non-small-cell lung cancer.

ABSTRACT: Objective:Neoadjuvant chemotherapy has increased the survival benefit of non-small cell lung cancer (NSCLC) patients. The effects of different neoadjuvant therapies are still controversial. We carried out the study to evaluate the efficacy and safety of neoadjuvant therapy. Methods:We performed a search of electronic databases (PubMed, Embase, MEDLINE, Cochrane) for randomized controlled trials (RCTs) comparing neoadjuvant treatment. After literature screening and data extraction, efficacy, and safety were analyzed by the Bayesian network meta-analysis (NMA). Results:A total of 19 RCTs were included, covering 3276 patients and six kinds of neoadjuvant therapies, including immunotherapy, targeted therapy, chemotherapy drugs and radiotherapy. Erlotinib, the first-generation epidermal growth factor receptor t?yrosine inhibitors (EGFR TKIs), neoadjuvant targeted therapy is best for improving overall survival (OS) and progression-free survival (PFS), which is superior to other neoadjuvant therapy, such as neoadjuvant chemotherapy with platinum drugs [hazard ratio (HR) 0.39, 95% confidence intervals (CIs) 0.16-0.96], neoadjuvant chemoradiotherapy (HR 0.37, 95% CI 0.14-0.96) and neoadjuvant chemotherapy with non-platinum drugs (HR 0.25, 95% CI 0.07-0.90). OS of all neoadjuvant therapies is superior to surgery alone, but only neoadjuvant chemotherapy with platinum drugs showed a significant advantage (HR 0.76, 95% CI 0.59-0.93). Besides, for the stage IIIA N2 NSCLC patients, no significant difference was found between neoadjuvant therapies. Conclusions:Targeted neoadjuvant therapy is the best treatment for prolonging PFS. The neoadjuvant chemotherapy with platinum drugs was associated with the better OS benefits for patients with NSCLC, compared with surgery alone. There is no significant difference in the efficacy of neoadjuvant therapy for the stage IIIA N2 NSCLC.

SUBMITTER: Ren Y

PROVIDER: S-EPMC7675866 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Bayesian network meta-analysis of efficacy and safety of neoadjuvant therapy for non-small-cell lung cancer.

Ren Yijiu Y Tang Hai H Zhang Jie J She Yunlang Y Sun Xiaoting X Xie Dong D Chen Chang C

Therapeutic advances in medical oncology 20201116

<h4>Objective</h4>Neoadjuvant chemotherapy has increased the survival benefit of non-small cell lung cancer (NSCLC) patients. The effects of different neoadjuvant therapies are still controversial. We carried out the study to evaluate the efficacy and safety of neoadjuvant therapy.<h4>Methods</h4>We performed a search of electronic databases (PubMed, Embase, MEDLINE, Cochrane) for randomized controlled trials (RCTs) comparing neoadjuvant treatment. After literature screening and data extraction, ...[more]

PMID: 33240402

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Project description:BackgroundTargeted therapies have led to significant improvement in the management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). We performed a network meta-analysis of frontline treatment options of ALK-positive NSCLC to provide clinical guidance.MethodsPubMed, Embase, ClinicalTrials.gov, and international conference databases were searched to identify relevant trials from inception to June 30, 2021. Phase III randomized controlled trials (RCTs) comparing treatments for patients with ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcomes: progression-free survival (PFS), overall survival (OS), risk of the central nervous system (CNS) progression, adverse events (AEs) of grade (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for primary outcome of PFS and secondary outcome of OS and risk of CNS progression were obtained. A multivariate, consistency model, fixed-effects analysis was used in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration's tool.ResultsNine RCTs comprising 2,484 patients were included with seven treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) significantly prolong PFS and reduced risk of CNS progression except for ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs.ConclusionsLorlatinib is associated with the highest PFS benefit and lowest risk of CNS progression benefits for patients with advanced ALK-positive NSCLC, compared with other first-line treatments, but with higher toxicity. The implementation of a newer generation of ALK-TKIs in the first-line treatment of ALK-positive NSCLC into current clinical practice is evolving rapidly.

Project description:AimsCurrently, there are many approaches available for neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer that improve therapeutic efficacy but are also controversial. We conducted a two-step Bayesian network meta-analysis (NMA) to compare odds ratios (ORs) for pathologic complete response (PCR) and safety endpoints.MethodsThe Cochrane Central Register of Controlled Trials, PubMed, Embase, and online abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched comprehensively and systematically. Phase II/III randomised clinical trials for targeted therapy in at least one arm were included.ResultsA total of 9779 published manuscripts were identified, and 36 studies including 10,379 patients were finally included in our analysis. The NMA of PCR showed that dual-target therapy is better than single-target therapy and combination chemotherapy is better than monochemotherapy. However, anthracycline did not bring extra benefits, whether combined with dual-target therapy or single-target therapy. On the other hand, the addition of endocrine therapy in the HER2-positive, hormone receptor (HR)-positive subgroup might have additional beneficial effects but without significant statistical difference. By performing a conjoint analysis of the PCR rate and safety endpoints, we found that 'trastuzumab plus pertuzumab' and 'T-DM1 containing regimens' were well balanced in terms of efficacy and toxicity in all target regimens.ConclusionIn summary, trastuzumab plus pertuzumab-based dual-target therapy with combination chemotherapy regimens showed the highest efficacy of all optional regimens. They also achieved the best balance between efficacy and toxicity. As our study showed that anthracycline could be replaced by carboplatin, we strongly recommended TCbHP as the preferred choice for neoadjuvant treatment of HER2-positive breast cancer. We also look forward to the potential value of T-DM1 in improving outcomes, which needs further study in future trials.

Project description:PurposeThis systematic review with network meta-analysis compared the efficacy and safety of currently licensed second-line treatments in patients with late stage non-small cell lung cancer (NSCLC).MethodsRandomised controlled trials (RCTs) of participants with advanced/metastatic NSCLC receiving second/third line treatments were screened. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 to July, 2017. Two reviewers screened bibliographic records, extracted data, and assessed risk of bias of included studies. The outcomes were overall survival (OS), progression-free survival (PFS), and drug-related grade 3-5 adverse-events (AEs). We pooled study-specific hazard ratios (HR; for OS and PFS) and risk ratios (RR; for AEs) using conventional and network-meta-analyses, and ranked interventions by the surface under the cumulative ranking curve.FindingsWe included 11 RCTs (7,581 participants) comparing nine drugs. All drugs except for erlotinib significantly improved OS compared to docetaxel. Nivolumab was the highest ranking drug followed by atezolizumab and pembrolizumab. There was no significant difference in OS across these three drugs (HR = 0.98, 95% CI 0.79, 1.21 for nivolumab vs atezolizumab; HR = 0.98, 95% CI 0.77, 1.25 for nivolumab vs pembrolizumab). For PFS, ramucirumab + docetaxel and nivolumab were the drugs with the highest ranking. All interventions except ramucirumab + docetaxel had a reduced risk for severe drug-related AEs vs. docetaxel. Of the drugs with the highest ranking on AEs, nivolumab was significantly safer compared to atezolizumab (RR = 0.55, 95% CI 0.38, 0.79) or pembrolizumab (RR = 0.52, 95% CI 0.34, 0.81).ImplicationsNivolumab, pembrolizumab and atezolizumab exhibited superior benefit/risk balance compared to other licensed drugs used late stage NSCLC. Our results indicate that the use of immunotherapies in people diagnosed with non-specific late stage NSCLC should be promoted. The use of docetaxel may now be judged irrelevant as a comparator intervention for approval of new drugs for second line treatment of NSCLC.Study registration numberPROSPERO CRD42017065928.

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Bayesian network meta-analysis of efficacy and safety of neoadjuvant therapy for non-small-cell lung cancer.

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Bayesian network meta-analysis of efficacy and safety of neoadjuvant therapy for non-small-cell lung cancer.

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