Front-line therapy for brain metastases and non-brain metastases in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: a network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses.@*METHODS@#Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework.@*RESULTS@#This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively.@*CONCLUSION@#Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.

Current Progress and Future Developments of Antibody Drug Conjugates in Lung Cancer / 中国肺癌杂志

Antibody drug conjugates (ADCs) are a novel class of anti-cancer drugs, which combined the specificity of monoclonal antibodies with the cytotoxic palyload via the linkers. Many ADCs have not only verified impressive activity in a variety of cancers, including breast cancer and hematological system tumors, but also in lung cancer. The aim of this study was to provide informations for practice by summarizing the mechanism of action, clinical application and problems and challenges of ADCs.
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Clinical features of patients with EGFR mutation-positive non-small cell lung cancer and brain metastases / 中华放射肿瘤学杂志

Advanced non-small cell lung cancer (NSCLC) patients are commonly with brain metastases, leading to poor survival and quality of life. Epidermal growth factor receptor (EGFR) is common sensitive mutation type in NSCLC. Compared with other molecular types, it has different molecular biological characteristics. For patients with brain metastases and EGFR-mutated advanced NSCLC, EGFR-tyrosine kinase inhibitors can prolong overall survival and improve intracranial and extracranial control rate. To understand the characteristics of brain metastases of patients with sensitively EGFR-mutated NSCLC, the incidence, onset time, site, number and size of lesions, symptoms, targeted treatment effect and disease outcomes were reviewed, which can provide reference for interventional timing and local treatment technology selection of local treatment for brain parenchymal metastases.

Clinical Features of EGFR Mutation Negative in Patients with Non-small Cell Lung Cancer and Brain Metastases / 中国肺癌杂志

In addition to rare incidence of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 receptor kinase (ROS1) positive patients, patients with brain metastases of non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) sensitive mutation have no effective systemic therapy at present, and the overall prognosis is poor. Since the low blood-brain barrier permeability of chemotherapy drugs, the local treatment plays an important role in brain metastases. To understand the clinical characteristics and treatment of brain parenchymal metastases in patients with NSCLC and EGFR mutation negative, we reviewed the incidence, onset time, site, numbers, size, symptom, therapeutic effect and disease evolution in them, which can provide reference for interventional timing and local treatment technology selection of local treatment for brain parenchymal metastases.
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Review on Treatment Modalities for Resectable IIIa/N2 Non-small Cell Lung Cancer / 中国肺癌杂志

Standard treatment for resectable IIIa/N2 non-small-cell lung cancer (NSCLC) is still under debate. Optional treatments include chemotherapy, radiotherapy and surgery, other options include target therapy and immunotherapy. Multidisciplinary treatment has therefore been emphasized by various clinical trials, including bimodality strategy which has been defined as chemotherapy plus surgery or chemotherapy plus radiotherapy, and trimodality treatment which refers to chemotherapy plus surgery and radiotherapy. However, there is still no consensus on the optimal strategy on treating resectable IIIa/N2 NSCLC. Therefore, we reviewed a series of phase II and III clinical trials as well as some meta-analyses and case reports to compare the efficacy of different strategies on survival of cN2 NSCLC, and concluded that for resectable IIIa/N2 NSCLC surgery is recommended, and that strategy of chemotherapy plus surgery may not achieve better survival than that of chemotherapy plus radiotherapy. Size of tumor as well as lymph nodes should be taken into account when choosing optimal therapy, so that promising individualized strategy could be given to patients with resectable stage IIIa/N2 NSCLC.
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