【佳學(xué)基因靶向藥物基因檢測(cè)】原裝 EGFR-TKI 聯(lián)合貝伐珠單抗治療 EGFR-TKI 治療后逐漸進(jìn)展的晚期肺腺癌患者的療效和安全性：一項(xiàng)單組研究

國(guó)內(nèi)正規(guī)血管檢測(cè)機(jī)構(gòu)關(guān)鍵點(diǎn)

深研基因檢測(cè)機(jī)構(gòu)自我培訓(xùn)教材看到《Ann Transl Med》在?2022 Dec;10(24):1334.發(fā)表了一篇題目為《》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Jianlin Long,?Shuangyi Lei,?Zhijuan Wu,?Shuanglong Xiong,?Chunmei Wang,?Lumi Huang,?Guanzhong Liang,?Dan Yang,?Yan Teng,?Yongsheng Li,?Jun Qi,?Dairong Li等完成。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。

腫瘤基因檢測(cè)及靶向藥物治療研究關(guān)鍵詞：

非小細(xì)胞肺癌 (NSCLC),抗血管生成,耐藥性;靶向治療,酪氨酸激酶抑制劑 (TKI)。

腫瘤治療檢測(cè)基因臨床應(yīng)用結(jié)果

靶向藥物研究立項(xiàng)的依據(jù)：維持原有的表皮生長(zhǎng)因子受體酪氨酸激酶抑制劑（EGFR-TKI）治療是漸進(jìn)性EGFR陽(yáng)性轉(zhuǎn)移性非小細(xì)胞肺癌（NSCLC）的標(biāo)準(zhǔn)治療。血管生成通路可導(dǎo)致 EGFR-TKI 耐藥，但該組聯(lián)合策略的有效性仍有爭(zhēng)議。本研究旨在評(píng)估原始 EGFR-TKI 聯(lián)合貝伐珠單抗在真實(shí)世界環(huán)境中經(jīng)歷逐漸進(jìn)展的攜帶 EGFR 突變的晚期和轉(zhuǎn)移性肺腺癌患者中的療效和安全性。佳學(xué)基因解碼的途徑：從 2019 年 6 月到 2021 年 12 月，中國(guó)重慶大學(xué)腫瘤醫(yī)院確定了 35 例轉(zhuǎn)移性 EGFR 陽(yáng)性 NSCLC 患者在 EGFR-TKI 治療后逐漸進(jìn)展，并接受原始 TKI 聯(lián)合貝伐珠單抗治療。所有患者在治療前均經(jīng)再次活檢證實(shí)為EGFR陽(yáng)性?；颊咴谥饾u進(jìn)展后接受 EGFR-TKI 和貝伐珠單抗（15 mg/kg Q3W）治療，直至快速進(jìn)展或出現(xiàn)無(wú)法耐受的毒性。總生存期（overall survival，OS）、無(wú)進(jìn)展生存期1（progression-free survival 1，PFS1，從開始EGFR-TKI治療到疾病快速進(jìn)展的時(shí)期）、PFS2（從開始EGFR-TKI聯(lián)合貝伐珠單抗治療到疾病快速進(jìn)展的時(shí)期）收集并分析聯(lián)合治療的疾病進(jìn)展情況、疾病控制率（DCR）、不良事件發(fā)生情況。靶向藥物研究的客觀數(shù)據(jù)：共33例患者可參與療效評(píng)價(jià)。中位 PFS1 和 PFS2 分別為 20.5 個(gè)月和 8 個(gè)月； DCR為93.94%；中位 OS 不成熟。多變量Cox比例風(fēng)險(xiǎn)模型顯示吸煙狀態(tài)[風(fēng)險(xiǎn)比（HR）=3.692，95%置信區(qū)間（CI）：1.450-9.404，P=0.006]，聯(lián)合EGFR T790M突變或罕見(jiàn)突變（HR=2.480，95% CI ：1.073-5.729，P=0.034）和惡性胸腔積液（HR=3.707，95%CI：1.460-9.414，P=0.006）是PFS2的獨(dú)立危險(xiǎn)因素。賊常見(jiàn)的大于 3 級(jí)的治療相關(guān)不良事件包括高血壓 (23.7%)、蛋白尿 (8.3%) 以及丙氨酸氨基轉(zhuǎn)移酶 (ALT; 4.1%) 和天冬氨酸氨基轉(zhuǎn)移酶 (AST; 2.9%) 升高。藥物指導(dǎo)及病因判斷的依據(jù)：連續(xù)原始 TKI聯(lián)合貝伐珠單抗顯示出部分良好的療效和安全性，可能代表轉(zhuǎn)移性 EGFR 突變 NSCLC 患者在 EGFR-TKI 治療后逐漸進(jìn)展的治療選擇?？寡苌桑荒退幮?靶向治療；酪氨酸激酶抑制劑 (TKI)。

腫瘤發(fā)生與革命國(guó)際數(shù)據(jù)庫(kù)描述：

Background:?Keeping on original epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment is the standard treatment for gradual progression EGFR-positive metastatic non-small cell lung cancer (NSCLC). Angiogenic pathway can lead to EGFR-TKI resistance, but the effectiveness of combination strategies in this group is still controversial. This study aimed to assess the efficacy and safety of the original EGFR-TKI combined with bevacizumab in advanced and metastatic lung adenocarcinoma patients harboring EGFR-mutation who experience gradual progression in a real-world setting.Methods:?From June 2019 to December 2021, a total of 35 metastatic EGFR positive NSCLC patients experienced gradual progression after EGFR-TKI treatments and received original TKI combined with bevacizumab were identified at Chongqing University Cancer Hospital, China. All patients were confirmed EGFR positive by rebiopsy before treatment. Patients were treated with EGFR-TKI and bevacizumab (15 mg/kg Q3W) after gradual progression until rapid progression or intolerable toxicity. The overall survival (OS), progression-free survival 1 (PFS1, period from the beginning of EGFR-TKI treatment to the rapid progression of the disease), PFS2 (period from the beginning of EGFR-TKI combined with bevacizumab treatment to the rapid progression of the disease), disease control rate (DCR), and adverse events of the combined treatment were collected and analyzed.Results:?A total of 33 patients could participate the efficacy evaluation. Median PFS1 and PFS2 were 20.5 and 8 months, respectively; DCR was 93.94%; median OS was immature. Multivariate Cox proportional hazards model showed that smoking status [hazard ratio (HR) =3.692, 95% confidence interval (CI): 1.450-9.404, P=0.006], combined EGFR T790M mutation or rare mutation (HR =2.480, 95% CI: 1.073-5.729, P=0.034), and malignant pleural effusion (HR =3.707, 95% CI: 1.460-9.414, P=0.006) were independent risk factors for PFS2. The most common treatment-related adverse events greater than grade 3 included hypertension (23.7%), proteinuria (8.3%), and increased alanine aminotransferase (ALT; 4.1%) and aspartate aminotransferase (AST; 2.9%).Conclusions:?Continuous original TKI combined with bevacizumab showed partly favorable efficacy and safety and may represent a therapeutic option for metastatic EGFR-mutation NSCLC patients experiencing gradual progression after EGFR-TKI treatment.Keywords:?Non-small cell lung cancer (NSCLC); anti-angiogenesis; drug resistance; targeted therapy; tyrosine kinase inhibitor (TKI).