Bevacizumab plus erlotinib in Chinese patients with untreated,EGFR-mutated,advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study

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酪氨酸激酶抑制剂联合放疗对鼻咽癌裸鼠移植瘤的作用

目的：探讨酪氨酸激酶抑制剂 Erlotinib 联合放疗对鼻咽癌裸鼠移植瘤的作用。方法将鼻咽癌细胞株 CNE2接种于32只裸鼠后腿皮下,8 d 后肿瘤体积在100～200 mm 3之间,将裸鼠按体积大小随机分为4组：对照组、Erlotinib 组、放疗组和放疗＋Erlotinib 组,每组8只。分组第1天予以照射1次8 Gy,Erlotinib 分组第1天予以灌胃给药,1.6 mg／次,1次／d,连用2周。停药1周后处死动物,测量瘤块体积和重量,采用免疫组织化学法检测各组标本中 EGFR 和 p －EGFR 的表达情况,并进行统计学分析。结果对照组、Erlotinib 组、放疗组、放疗＋Erlotinib 组的瘤重分别为（2.60±1.51）、（1.56±0.67）、（0.71±0.42）、（0.48±0.31）g,放疗＋Erlotinib 组瘤重小于 Erlotinib 及放疗组（P ＝0.026,P ＝0.047）。各组 EGFR 表达无明显差异,p －EGFR 在放疗组明显增强,放疗＋Erlotinib 组阳性表达率最低。结论Erlotinib 通过抑制 EGFR 磷酸化增强了鼻咽癌的放射敏感性。     

Assessing the benefit–risk of new treatments using generalised pairwise comparisons: the case of erlotinib in pancreatic cancer

Background:

Efficacy and safety are the two considerations when characterising the effects of a new therapy. We sought to apply an innovative method of assessing the benefit–risk balance using data from a completed randomised controlled trial that compared erlotinib vs placebo added to gemcitabine in patients with advanced pancreatic cancer (NCIC CTG PA.3).

Methods:

We applied generalised pairwise comparisons with several prioritised outcome measures (e.g., one or more benefit outcomes and one or more risk outcomes). Here, the first priority outcome was overall survival (OS) time. Differences in OS that exceeded 2 months were considered clinically meaningful. The second priority outcome was toxicity. The overall treatment effect was quantified using the proportion in favour of erlotinib, which can be interpreted as the net proportion of patients who have a better overall outcome with erlotinib as compared with placebo. Sensitivity analyses were performed.

Results:

In this trial 569 patients were randomly assigned in a 1 : 1 ratio to receive gemcitabine plus either erlotinib or a matched placebo. Overall, the method indicated no statistically significant overall treatment effect in favour of erlotinib; if anything, the point estimate of the net proportion leaned in favour of the placebo group (overall proportion in favour of erlotinib=−3.6%, 95% CI, −14.2– 7.1% P=0.51). The net proportion was never in favour of the erlotinib group throughout all sensitivity analyses.

Conclusions:

Generalised pairwise comparisons make it possible to assess the benefit–risk balance of new treatments using a single statistical test for any number of prioritised outcomes. The benefit–risk assessment was not in favour of adding erlotinib to gemcitabine for the treatment of patients with advanced pancreatic cancer.     

EGF receptor tyrosine kinase inhibitors in the treatment of brain metastases from non-small-cell lung cancer

The incidence of brain metastasis (BM) is high in patients with non-small-cell lung cancer. Available standard therapeutic options, such as whole-brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. Novel agents, such as EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs), have now been included in standard non-small-cell lung cancer treatments. In a small subset of patients harboring EGFR-activating mutations, erlotinib and gefitinib administration was followed by a response rate of 70–80%, and a longer progression-free and overall survival than those obtained with standard chemotherapeutic regimens. However, since most of the larger studies on these agents have excluded BM patients from their series, few prospective data are available on the efficacy of these agents in this setting. In recent years, however, several authors have reported a growing number of cases of partial and complete response in BM patients treated with EGFR TKIs. Data from retrospective series and Phase II studies also suggest that a response can be obtained using EGFR TKI treatment for patients with BM, especially those harboring EGFR mutations.     

Personalized medicine for non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is a heterogeneous illness associated with a high mortality rate. Personalized therapy may improve treatment outcomes by identification of a specific genotypic anomaly and target-specific therapy. The most significant development in recent years was the discovery of activated EGF receptor (EGFR) mutations at exons 19 and 21. Patients with EGFR mutations respond dramatically to EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib, resulting in longer progression-free survival. Multiple randomized studies, including the Iressa Pan-Asia Study and WJTOG3405, have confirmed the role of EGFR tyrosine kinase inhibitors as standard first-line therapy for patients with the EGFR mutation. In this article, we summarize the current nonpersonalized therapies and examine the available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, or metastatic disease.