VCD/IE方案联合阿帕替尼治疗化疗失败进展期尤因肉瘤的回顾性研究

目的：评估VCD/IE方案（长春新碱+环磷酰胺+多柔比星与异环磷酰胺+依托泊苷交替）联合阿帕替尼治疗化疗失败进展期尤因肉瘤的疗效与安全性。方法：回顾性研究2017年1月至2021年12月于华中科技大学同济医学院附属协和医院,接受VCD/IE方案联合阿帕替尼治疗化疗失败的进展期尤因肉瘤11例患者的临床资料。与同期接受阿帕替尼单药治疗的尤因肉瘤患者对比,评估该方案的疗效及安全性。主要观察终点为疾病无进展生存期（progression-free survival,PFS）,次要观察终点为客观缓解率（objective response rate,ORR）、疾病控制率（disease control rate,DCR）、总生存时间（overall survival,OS）和不良反应（adverse event,AE）。结果：共筛选出符合入排标准的联合治疗患者11例,阿帕替尼单药组10例。两组患者中位随访时间分别为19.5个月和14.5个月。其中男性占比分别为72.7%(8/11)和70%(7/10),平均年龄分别为18.1±6.7岁和20.8±15.7岁。VCD/IE方案联合阿帕替尼的ORR、...     

西妥昔单抗联合化疗治疗K-Ras野生型转移性结直肠癌的疗效分析

目的 观察西妥昔单抗联合化疗治疗K-Ras野生型转移性结直肠癌的疗效及安全性,探讨可能影响疗效及预后的因素。方法 收集2007年5月至2012年5月解放军总医院收治的K Ras野生型转移性结直肠癌患者共90例,采用西妥昔单抗（400mg／m2,静滴,第1周,维持剂量每周250mg／m2或每2周500mg／m2）联合化疗方案,主要为含伊立替康为基础方案（FOLFIRI或XELIRI或单药CPT-11）、含奥沙利铂为基础方案（FOLFOX或XELOX）、5 FU／LV方案或单药卡培他滨。回顾性评估西妥昔单抗联合化疗在治疗中的疗效和安全性,分析患者临床病理特征,并探讨影响疗效的因素以及此类患者预后相关的因素。结果 西妥昔单抗中位治疗时间为16周（6～44周）,客观缓解率（ORR）为45.6％,疾病控制率（DCR）为87.8％。其中一线治疗ORR为51.6％,二线治疗ORR为40.0％,三线治疗ORR为18.2％。单因素分析显示,年龄、原发灶部位、西妥昔单抗治疗时间与疗效有关,差异具有统计学意义（P＜0.05）。90例患者中位随访时间为20.2个月,82例（91.1％）复发转移,60例（66.7％）死亡。患者中位无疾病进展时间（PFS）为7.8个月,中位总生存时间（OS）为22.5个月。其中一线中位PFS为9.1个月,中位OS为27.6个月;二线中位PFS为7.7个月,中位OS为14.5个月;三线中位PFS为2.9个月,中位OS为6.7个月。单因素分析显示：原发灶部位、早期肿瘤缓解者以及西妥昔单抗治疗时间与PFS有关;原发灶部位、早期肿瘤缓解者、西妥昔单抗治疗时间以及转移侵及范围与OS有关。Cox多因素生存分析显示：原发肿瘤病灶部位、早期肿瘤缓解是PFS的独立预后因素,转移侵及范围是OS的独立预后因素。西妥昔单抗相关治疗最常见的不良反应是痤疮样皮疹（78.0％）,化疗相关的不良反应主要为腹泻、恶心呕吐、骨髓抑制,经对症处理后,患者均可耐受。结论 西妥昔单抗联合多种方案化疗治疗晚期转移性结直肠癌患者,各线治疗均能取得较好的疗效,不良反应可耐受;原发灶部位可能是西妥昔单抗联合化疗的疗效预测因素,其与患者预后生存可能相关;早期肿瘤缓解可作为判断患者预后相关指标。     

多西他赛为主与奥沙利铂为主一线治疗晚期Lauren分型胃癌的疗效对比

目的 探讨以多西他赛为主的化疗方案与以奥沙利铂为主的化疗方案一线治疗晚期胃癌在Lauren分型中的临床疗效。方法 收集中国人民解放军总医院311例晚期胃癌患者,对有随访结果的199例进行Lauren分型,其中肠型88例,弥漫型105例,混合型6例。一线以多西他赛为主化疗方案的109例,以奥沙利铂为主化疗方案的54例,其他化疗方案36例。中位可评价周期数为4周期,且疗效可评价。结果 在肠型组中以多西他赛为主化疗的客观有效率（ORR）为26.7%,疾病控制率（DCR）为86.7%,中位疾病无进展期（mPFS）为4.50月,中位总生存期（mOS）为15.67月;在肠型组中以奥沙利铂为主化疗的客观有效率（ORR）为15.0%,疾病控制率（DCR）为85.0%,中位疾病无进展期（mPFS）为6.33月,中位总生存期（mOS）为21.50月。在弥漫型组中以多西他赛为主化疗的客观有效率（ORR）为18.9%,疾病控制率（DCR）为67.9%,中位疾病无进展期（mPFS）为2.53月,中位总生存期（mOS）为7.23月;在弥漫型组中以奥沙利铂为主化疗的客观有效率（ORR）为10.7%,疾病控制率（DCR）为67.9%,中位疾病无进展期（mPFS）为3.57月,中位总生存期（mOS）为7.23月。因混合型病例较少,故未列入统计之列。结论 弥漫型胃癌较肠型胃癌的预后差。以多西他赛为主化疗方案和以奥沙利铂为主化疗方案在胃癌Lauren分型的肠型和弥漫型中ORR、DCR、mPFS以及mOS的比较,差异均无统计学意义（P＞0.05）。     

EGFR-TKI治疗后缓慢进展的晚期NSCLC患者原药维持联合阿帕替尼的疗效及安全性

目的:观察一代EGFR-TKI治疗后缓慢进展的晚期NSCLC患者继续原药联合阿帕替尼的疗效及安全性。方法:收集2016年9月至2018年7月于大连医科大学附属第二医院肿瘤内科就诊的29例经一代EGFR-TKI单药治疗后缓慢进展（疾病控制≥6个月，与以往评估相比，肿瘤负荷较前轻度增加 2分，症状评分 1分），继续原药维持联合阿帕替尼(250 mg／日1次)的晚期NSCLC患者的病例资料，观察客观缓解率（ORR）、疾病控制率（DCR）、中位无进展生存期（mPFS）及不良反应情况。结果:29例患者中，ORR为13.8%，DCR为86.2%，mPFS为5.470个月（95%CI 4.367~6.573个月）；常见的药物相关毒性反应是高血压、乏力和蛋白尿，经治疗后症状改善；其中4例经联合治疗一段时间后，临床症状稳定，出现病灶增大，但未达到疾病进展的患者，未换其他治疗方案，而是将阿帕替尼的用量加至500 mg／日1次，病灶再次稳定或缩小；L858R突变患者的mPFS比19号外显子缺失者显著延长，差异有统计学意义（P=0.011）。结论:一代EGFR-TKI治疗后缓慢进展的晚期NSCLC患者原药维持联合阿帕替尼治疗有效，且具有可接受可控的毒副作用。     

晚期胃癌不同一线及后线治疗方案的疗效对比分析北大核心

目的:分析晚期胃癌(advanced gastric cancer, AGC)一线及后线治疗方案的疗效及生存情况,为指导AGC的系统治疗及全程管理提供依据。方法:收集我院肿瘤科2015年01月至2019年12月收治的AGC患者的临床特征、辅助检查资料、治疗相关资料、疗效评估、疾病转归等相关临床资料,建立数据库,分析不同一线及后线治疗方案的疗效,以及不同人群、进行不同线数化疗的患者总生存期(overall survival, OS)的差异。结果:一线治疗总体客观缓解率(objective response rate, ORR)为37.6%,疾病控制率(disease control rate, DCR)为83.9%;二线治疗ORR为9.5%,DCR为44.6%;三线及以上治疗ORR为0%,DCR为15.2%。总体人群一线治疗中位无进展生存(median progression-free survival, mPFS)时间为7.0个月,中位总生存(medianoverall survival,mOS)时间为15.6个月;二线治疗mPFS时间为3.0个月,mOS时间为7.2个月。一线化疗采取含铂方案与含紫杉方案对比,mPFS分别为7.0个月、4.5个月(P=0.041),mOS分别为16.0个月、9.0个月(P=0.061);二线含紫杉方案与含伊立替康方案对比,mPFS分别为2.6个月、4.0个月(P=0.531),mOS分别为7.0个月、6.5个月(P=0.822)。仅进行一线治疗、一线+二线治疗、一线+二线+三线及以上治疗的AGC患者mOS分别为14.0个月、14.0个月及20.0个月,进行三线及以上治疗的患者mOS优于进行一线+二线治疗的患者(P=0.001)。一线方案中采用两药或三药及以上、有无免疫治疗对患者的mPFS及mOS无影响,且二线治疗中有无联合免疫治疗对患者的mPFS及mOS也无影响。结论:含铂双药方案疗效较佳,应作为AGC患者一线治疗的优选方案;二线及后线化疗有效率较低,二线化疗方案紫杉类与伊立替康疗效无差异;在非选择AGC人群中,一线及二线治疗中联合免疫治疗未见改善生存,化疗仍然是基石。     

甲磺酸阿帕替尼二线治疗晚期胆囊癌的疗效与安全性分析

目的:评估甲磺酸阿帕替尼二线治疗晚期胆囊癌的有效性和安全性。方法:选取2015年5月至2017年5月晚期胆囊癌一线治疗失败的患者60例,根据治疗方法分为对照组30例及治疗组30例,对照组采用吉西他滨治疗,治疗组采用甲磺酸阿帕替尼治疗。以患者的疾病控制率（disease control rate,DCR）、客观缓解率（objective remission rate,ORR）、中位无疾病进展生存期（median progressive free survival,mPFS）及中位总生存时间（median overall survival,mOS）为主要研究终点,通过电话方式进行随访,随访时间为1年。结果:治疗组与对照组DCR为46.7% vs 13.3%,具有显著统计学差异（P=0.005）;其ORR为30.0% vs 3.3%,具有显著统计学差异（P=0.006）。治疗组与对照组的mPFS分别为2.5个月（95%CI:2.311~2.689） vs 1.6个月（95%CI:1.439~1.761）,差异具有统计学意义（P=0.017）;mOS分别为4.6个月（95%CI:4.406~4.794）和3.8个月（95%CI:3.438~4.162）,差异具有统计学意义（P=0.019）。治疗组主要的毒副反应为手足综合征8例（26.7%）、蛋白尿6例（20.0%）及高血压12例（40.0%）;对照组主要的毒副反应为恶心呕吐14例（46.7%）、腹泻7例（23.3%）及中性粒细胞减少17例（56.7%）。治疗过程中,两组尚未出现Ⅳ级毒副反应及药物相关不良事件。结论:该研究表明,甲磺酸阿帕替尼在二线治疗晚期胆囊癌患者中优于吉西他滨单药治疗,其毒副反应可控。需要进一步进行大样本研究,探索更为有效的二线治疗方案,以期改善此类人群的临床结果。     

Clinical outcomes to pemetrexed-based versus non-pemetrexed-based platinum doublets in patients with KRAS-mutant advanced non-squamous non-small cell lung cancer

KRAS mutation has been associated with enhanced dependency on the folate metabolism in preclinical studies. However, whether KRAS mutation correlates to increased sensitivity to pemetrexed in patients with advanced NSCLC is unknown. Patients with advanced non-squamous NSCLC who had a documented EGFR and ALK WT genotype with simultaneous KRAS mutation assessment were evaluated for clinical outcome to pemetrexed- and non-pemetrexed-based first-line platinum doublet according to KRAS mutation status. Of 356 patients identified, 138 harbored a KRAS mutation. Among KRAS-mutant NSCLCs, those treated with platinum/pemetrexed (81/138) had significantly lower ORR (30.9% versus 47.4%, P = 0.05), DCR (51.8% versus 71.9%, P = 0.02) and shorter median progression-free survival [mPFS 4.1 versus 7.1 months, HR 1.48 (95% CI 1.03–2.12), P = 0.03] and median overall survival [mOS 9.7 versus 26.9 months, HR 1.93 (95% CI 1.27–2.94), P = 0.002] compared to those who received a non-pemetrexed-based platinum doublet (57/138). No difference in ORR, DCR, mPFS and mOS was observed between KRAS WT patients who received a pemetrexed-based (124/218) versus non-pemetrexed base platinum doublets (94/218). After adjusting for performance status, age and the presence of brain metastasis at baseline, treatment with pemetrexed-based platinum doublet was associated with an increased risk of death [HR 2.27 (95% CI 1.12–4.63), P = 0.02] among KRAS-mutant patients in multivariate analysis. Patients with KRAS-mutant lung adenocarcinoma have a poorer outcome on pemetrexed-based first-line chemotherapy. Whether KRAS-mutant NSCLCs should be excluded from pemetrexed-containing regimens should be assessed prospectively.     

Special issue “The advance of solid tumor research in China”: Real-world clinical outcomes of alectinib for advanced nonsmall-cell lung cancer patients with ALK fusion in China

Global phase 3 trials have demonstrated the priority of several next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). However, clinical studies are conducted with specific populations that differ from the real world. The study aimed to evaluate the clinical outcomes of alectinib in real-world settings. Patients with advanced nonsmall-cell lung cancer (NSCLC) and EML4-ALK fusion were enrolled from two medical centers between June 2018 and June 2020. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) to alectinib. The secondary endpoint was response of brain metastases. The risk factors for disease progression were also investigated. In total, 127 patients with advanced NSCLC were enrolled into this study. Of them, 54.3% received first-line alectinib. The 1- and 2-year PFS rates were 77.4% and 68.3%, respectively. ORR and disease control rate (DCR) were 53.5% and 91.3%, respectively. Among patients with brain metastases, intracranial ORR and DCR were 63.6% and 88.6%, respectively. In addition, we found that “crizotinib pretreatment”, “liver metastasis” and “TP53 co-mutation” were individually associated with shorter PFS in alectinib treatment. In conclusion, this study confirms the salient clinical outcomes of alectinib for ALK-fusion-driven NSCLC patients with or without brain metastases, adding real-world evidence to the priority of alectinib in clinical practice.     

EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non–Small Cell Lung Cancer

BackgroundEpidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20-ins) mutations are an uncommon and heterogeneous group of non–small cell lung cancers (NSCLCs), resistant to conventional EGFR tyrosine kinase inhibitors (TKIs). Characteristics and outcomes of patients with EGFR ex20-ins have not been fully established; we sought to clarify them using a multinational patient database.Patients and MethodsPatients with NSCLC from six Australian institutions with EGFR exon 20 mutations (ex20-mut), excluding T790M, were retrospectively reviewed. Clinical characteristics and outcomes with systemic treatments were collected and analyzed using comparative statistics.ResultsAmong 109 patients with ex20-mut, 61% were females and 75% were Caucasians. More males presented with de novo metastatic disease (84% vs. 51%; P = .002). Central nervous system (48%) and liver (24%) metastases were common within metastatic patients (n = 86). Thirty-nine patients received platinum-based chemotherapy (PBC) and achieved a 43% objective response rate (ORR), median progression-free survival (mPFS) of 6.9 months, and median overall survival (mOS) of 31.0 months. Twenty-three of the patients with ex20-ins received conventional TKIs, resulting in an ORR of 13%, mPFS of 3.4 months (95% confidence interval [CI], 1.91-6.25), and mOS of 31.0 months (95% CI, 15.09-not reached). Nine patients with S786I mutations received TKIs, resulting in an ORR of 50%, mPFS of 18.2 months (2.79-not reached), and mOS of 33.4 months (95% CI, 16.14-not reached). Twenty-three patients received immune checkpoint inhibitor monotherapy (ICIm), resulting in an ORR of 4%, mPFS of 2.6 months (95% CI, 1.91-4.83), and mOS of 30.8 months (95% CI, 17.62-41.62).ConclusionAlthough phenotypically similar to patients with common EGFR mutations, patients with EGFR ex20-mut had worse survival, perhaps due to the lack of targeted therapies. Chemotherapy was superior to conventional EGFR TKIs in patients with EGFR ex20-ins, although there was moderate activity of TKIs in S768I mutations. ICIm was ineffective.     

阿帕替尼后线治疗晚期食管鳞癌患者的疗效及安全性

目的 探讨阿帕替尼后线治疗晚期ESCC患者的疗效和安全性.方法 纳入56例后线接受阿帕替尼单药治疗的晚期ESCC患者.阿帕替尼治疗的起始剂量为每天500 mg或250 mg.分析患者的临床病理资料、不良反应及预后.研究主要终点为无进展生存期(PFS),次要终点为客观缓解率(ORR)、疾病控制率(DCR)、总生存期(OS...     

真实世界中阿帕替尼后线治疗胃癌的疗效观察及预后相关因素分析

目的:评估阿帕替尼在晚期胃癌患者中的疗效和安全性,寻找与预后相关的临床特征因素。方法:回顾性分析2014年12月至2019年6月收治的153例服用阿帕替尼治疗晚期胃癌的患者临床资料。观察指标为客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)、无进展生存期(progression-free survival,PFS)、总生存期(overall survival,OS)和治疗相关不良反应发生率。结果:总体纳入患者的ORR为6.9%,DCR为44.8%,中位PFS(median PFS,mPFS)为3.1个月(95% 2.863~3.337),中位OS(median OS,mOS)为6.0个月(95%CI 4.392~7.608)。3级及以上不良反应的发生率为47.6%(60/126),其中61.7%(37/60)的患者因此中止治疗。Logistic多因素回归分析显示,转移灶数目≤2个(P=0.008)、存在肝转移(P=0.007)、用药前确诊患癌时间＞1年(P=0.032)、联合全身治疗(P=0.036)是DCR的独立预后因素。COX多因素回归分析显示,用药前确诊患癌时间＞1年(P=0.016)、病理见低黏附性癌成分(P=0.001)、用药4周内耐受良好不发生3级及以上不良反应(P=0.009)是PFS延长的独立预后因素。转移灶数目≤2个(P=0.007)、骨髓抑制程度在2度及2度以下(P=0.014)是OS延长的独立预后因素。结论:阿帕替尼治疗晚期胃癌患者有效、安全可控,转移灶数目、肝转移等临床特征信息可以帮助医生判断预后。     

埃克替尼治疗98例复治EGFR突变阳性的晚期肺腺癌的疗效分析

目的:观察埃克替尼治疗复治表皮生长因子受体(epidermal growth factor receptor,EGFR）敏感突变的晚期肺腺癌患者的疗效及不良反应。方法:收集2011年11月至2016年7月期间一线或多线化疗进展的98例EGFR 敏感突变的晚期肺腺癌患者应用埃克替尼治疗的疗效、不良反应及生存资料。结果:98例既往化疗失败的EGFR基因敏感突变晚期肺腺癌患者中,达到完全缓解（CR）1例（1.0%）,部分缓解（PR）66例（67.3%）,疾病稳定（SD）20例（20.4%）,疾病进展（PD）11例（11.2%）;客观缓解率（ORR）为68.4%（67/98),疾病控制率（DCR）为88.8%（87/98）,中位无进展时间（mPFS）为8.8个月（95%CI:7.1～10.5个月）,中位生存时间（mOS）为15.5个月（95%CI:11.8～19.2个月）。亚组分析中,19外显子缺失突变患者的ORR（82.0% vs 54.2%,P=0.003）、mPFS（11.0个月 vs 6.0个月,P=0.008）及mOS（20.0个月 vs 12.6个月,P=0.016）均优于21外显子L858R突变患者;非脑转移患者的mOS优于脑转移患者（16.0个月 vs 8.0个月,P=0.039）;不吸烟患者的ORR 优于吸烟患者（76.7% vs 55.3%,P=0.023）;不同性别、年龄、肺癌分期、治疗线数、转移器官数对预后的影响均未见差异有统计学意义。不良反应以皮疹、腹泻、肝功能异常为主,经对症处理后症状均可明显缓解。结论:埃克替尼治疗既往化疗失败的EGFR突变阳性的晚期肺腺癌患者取得了确切的疗效,且不良反应发生率低。     

Multicenter phase II study of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis

ObjectiveBreast cancer (BC) with chest wall metastasis (CWM) usually shows rich neovascularization. This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2 (HER2)-negative advanced BC involving CWM.MethodsThis trial involved four centers in China and was conducted from September 2016 to March 2020. Patients received apatinib 500 mg/d [either alone or with endocrine therapy if hormone receptor-positive (HR+)] until disease progression or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint.ResultsWe evaluated 26 patients for efficacy. The median PFS (mPFS) and median overall survival (mOS) were 4.9 [range: 2.0−28.5; 95% confidence interval (95% CI): 2.1−8.3] months and 18 (range: 3−55; 95% CI: 12.9−23.1) months, respectively. The objective response rate (ORR) was 42.3% (11/26), and the disease-control rate was 76.9% (20/26). In the subgroup analysis, HR+ patients compared with HR-negative patients had significantly improved mPFS of 7.0 (95% CI: 2.2−11.8) monthsvs. 2.3 (95% CI: 1.2−3.4) months, respectively (P=0.001); and mPFS in patients without or with chest wall radiotherapy was 6.4 (95% CI: 1.6−19.5) monthsvs. 3.0 (95% CI: 1.3−4.6) months, respectively (P=0.041). In the multivariate analysis, HR+ status was the only independent predictive factor for favorable PFS (P=0.014). ConclusionsApatinib was highly effective for BC patients with CWM, especially when combined with endocrine therapy. PFS improved significantly in patients with HR+ status who did not receive chest wall radiotherapy. However, adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.     

Clinicopathologic and Genomic Factors Impacting Efficacy of First-Line Chemoimmunotherapy in Advanced NSCLC

IntroductionAlthough programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become a mainstay of first-line treatment for advanced NSCLC, factors associated with efficacy of chemoimmunotherapy (CIT) are not well characterized.MethodsIn this multicenter retrospective analysis, clinicopathologic and genomic data were collected from patients with advanced NSCLC (lacking sensitizing genomic alterations in EGFR and ALK) and evaluated with clinical outcomes to first-line CIT.ResultsAmong 1285 patients treated with CIT, a worsening performance status and increasing derived neutrophil-to-lymphocyte ratio in the blood were associated with a significantly reduced objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS). With increasing PD-L1 tumor proportion scores of less than 1%, 1% to 49%, 50% to 89%, and greater than or equal to 90%, there was a progressive improvement in ORR (32.7% versus 37.5% versus 51.6% versus 61.7%, p < 0.001), mPFS (5.0 versus 6.1 versus 6.8 versus 13.0 mo, p < 0.001), and generally mOS (12.9 versus 14.6 versus 34.7 versus 23.1 mo, p = 0.009), respectively. Of 789 NSCLCs with comprehensive genomic data, NSCLCs with a tumor mutational burden (TMB) greater than or equal to the 90th percentile had an improved ORR (53.5% versus 36.4%, p = 0.004), mPFS (10.8 versus 5.5 mo, p < 0.001), and mOS (29.2 versus 13.1 mo, p < 0.001), compared with those with a TMB less than the 90th percentile. In all-comers with nonsquamous NSCLC, the presence of an STK11, KEAP1, or SMARCA4 mutation was associated with significantly worse ORR, mPFS, and mOS to CIT (all p < 0.05); this was also observed in the KRAS-mutant subgroup of NSCLCs with co-occurring mutations in STK11, KEAP1, or SMARCA4 (all p < 0.05). In KRAS wild-type NSCLC, KEAP1 and SMARCA4 mutations were associated with a significantly shorter mPFS and mOS to CIT (all p < 0.05), but STK11 mutation status had no significant impact on mPFS (p = 0.16) or mOS (p = 0.38).ConclusionsIn advanced NSCLC, better patient performance status, low derived neutrophil-to-lymphocyte ratio, increasing PD-L1 expression, a very high TMB, and STK11/KEAP1/SMARCA4 wild-type status are associated with improved clinical outcomes to first-line CIT.     

UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN)

IntroductionApproximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.MethodsThis is a multicenter, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC treated with osimertinib as first EGFR inhibitor. The Response Evaluation Criteria in Solid Tumors and response assessment in neuro-oncology brain metastases brain objective response rate (ORR) were evaluated by the investigators. Median progression-free survival (mPFS), median overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Mutations found at resistance were collected.ResultsA total of 60 patients were included (22 centers, nine countries), with median age of 64 years, 75% females, and 83% Caucasian. The largest subgroups were G719X (30%), L861Q (20%), and de novo Thr790Met (T790M) (15%). The ORR was 61%, mPFS 9.5 months, mDOR 17.4 months, and median overall survival 24.5 months. Regarding patients with no concurrent common mutations or T790M (group A, n = 44), ORR was 60%, mPFS 8.6 months, and mDOR 11 months. For G719X, ORR was 47%, mPFS 8.8 months, and mDOR 9.1 months. For L861Q, ORR was 80%, mPFS 16 months, and mDOR 16 months. For de novo T790M, ORR was 44%, mPFS 12.7 months, and mDOR 46.2 months. Compound EGFRmut including common mutations had better outcome compared with only ucEGFRmut. For 13 patients with a response assessment in neuro-oncology brain metastases–evaluable brain metastases, brain ORR was 46%. For 14 patients, rebiopsy results were analyzed: four patients with additional EGFR mutation (C797S, D585Y, E709K), three with new TP53 mutation, one with c-Met amplification, one with PIK3CA mutation, and one with neuroendocrine transformation.ConclusionsOsimertinib was found to have an activity in ucEGFRmut with a high rate of disease control systemically and intracranially. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest data set of its kind.     

立体定向放疗联合或不联合经导管动脉化疗栓塞治疗不可切除结直肠癌肝转移的回顾性研究

目的:比较单纯立体定向放疗或经导管动脉栓塞化疗联合立体定向放疗治疗不可手术结直肠癌肝转移的疗效及安全性。 方法:回顾性分析23例不可手术结直肠癌肝转移患者资料,所有患者曾接受一线标准的全身化疗,化疗后肝脏病灶接受或者经导管动脉栓塞化疗。单纯接受立体定向治疗的13例患者为SBRT组,接受经导管动脉栓塞化疗和立体定向放疗的10例患者为TACE-SBRT组,比较两组患者的肝内病灶局部治疗后的疾病缓解率(RR)、疾病控制率(DCR)和疾病进展时间（TTP）,同时观察并发症发生情况,采用Kaplan-Meier、Log-rank检验,Cox回归模型分析中位无进展生存时间(mPFS)和总生存时间(mOS)。结果:SBRT组和TACE-SBRT组的局部治疗反应RR和DCR无统计学意义（P=0.685）;与SBRT组相比,TACE-SBRT组的无疾病进展时间延长,差异有统计学意义（11.77±1.56 vs 25.40±5.81,P=0.019）。TACE-SBRT的mPFS优于SBRT组,分别为17.4个月和15.1个月（P<0.05）,但是mOS两组之间无统计学意义。同时,仅有1例患者出现Ⅲ级肝功能损伤,治疗后恢复。Cox 回归比例风险模型分析确诊肝转移时CEA水平和同时性转移是无进展生存期和总生存期的预后不良因素(P<0.05)。结论:全身化疗后联合SBRT和TACE治疗不可切除的结直肠癌肝转移是一种安全有效的方法,是一种可接受的替代治疗方法,但仍需进一步研究。     

RALOX-HAIC联合免疫检查点抑制剂及靶向药物治疗中晚期肝癌的疗效分析

目的：探讨雷替曲塞+奥沙利铂方案肝动脉灌注化疗（RALOX-HAIC）联合免疫及靶向药物三联治疗中晚期肝细胞癌（hepatocellular carcinoma,HCC）的疗效与安全性。方法：回顾性分析2020年6月至2021年12月收治于南方医科大学南方医院39例行RALOX-HAIC联合靶免治疗的中晚期HCC患者,以首次HAIC治疗为起点,以患者疾病进展、死亡、不可耐受不良反应为终点,按照RECIST 1.1标准进行疗效评估,随访时间截至2022年10月。主要研究终点为客观缓解率（objective response rate,ORR）,次要研究终点为疾病控制率（disease control rate,DCR）、中位无进展生存期（median progression-free survival,mPFS）、中位总生存期（median overall survival,mOS）及安全性。结果：ORR为41.0%,DCR达87.2%,m PFS为7.3个月（95%CI:5.0～9.6）,mOS为14.6个月（95%CI:10.8～18.5）,其中1例患者成功转化行手术治疗后完全缓解至...     

安罗替尼联合阿霉素和异环磷酰胺治疗软组织肉瘤肺转移的疗效及安全性分析

目的：回顾性研究阿霉素和异环磷酰胺（adriamycin ifosfamide,AI）方案化疗联合安罗替尼维持治疗对软组织肉瘤肺转移患者的疗效与安全性。方法：收集天津医科大学肿瘤医院2018年6月至2022年4月软组织肉瘤肺转移接受AI方案化疗联合安罗替尼维持性治疗的32例患者。按照实体瘤疗效评价标准RECIST 1.1进行治疗效果评价,计算客观缓解率（objective response rate,ORR）及疾病控制率（disease control rate,DCR）,统计分析中位无进展生存期（median progression-free survival,mPFS）、中位总生存期（median overall survival,mOS）及相关不良事件。结果：32例软组织肉瘤肺转移患者中完全缓解（complete response,CR）1例（3.1%）,部分缓解（partial response,PR）10例（31.2%）,病情稳定（stable disease,SD）9例（28.1%）,疾病进展（progress disease,PD）12例（37.5%）,ORR为34.3%...     

培美曲塞单药与联合铂类药物二线治疗晚期非小细胞肺癌的临床观察

目的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)一线化疗有效率仅30%～40%。复发或初治无效患者的治疗,需引入新的药物及治疗方法。本试验观察培美曲塞单药或联合铂类二线治疗复发晚期NSCLC的疗效及毒副反应。方法回顾性分析经病理学或细胞学确诊的复发或转移性NSCLC腺癌患者共66例。其中应用培美曲塞单药治疗32例,培美曲塞联合铂类药物治疗34例。患者均接受2～4个周期该方案治疗。结果 66例患者均可评价疗效及毒副反应,CR 0例,PR 17例,SD 20例,PD 29例。其中单药组CR 0例、PR 7例、SD 10例、PD 15例,联合组CR 0例、PR 10例、SD 10例、PD 14例。单药与联合组的DCR(CR+PR+SD)、1年生存率、中位PFS、中位OS分别为53.1%和58.8%(P=0.64)、26.4%和35.3%(P=0.17)、2.5个月和2.7个月(P=0.09)、8.4个月和10.1个月(P=0.39),均无统计学差异。两组的主要不良反应均为白细胞减少、贫血和消化道反应。但老年组(≥65岁)亚组分析结果显示单药组的血液学毒性、消化道反应及皮疹的发生率均显著低于联合组。结论培美曲塞单药或联合铂类药物方案用于复发晚期NSCLC腺癌的二线治疗疗效和毒副反应均无显著性差异。培美曲塞单药对比联合铂类药物对于老年患者安全性更高。     

阿帕替尼单药在标准方案治疗失败晚期结直肠癌患者中的疗效及安全性

目的：探讨阿帕替尼单药在标准治疗方案失败晚期结直肠癌（colorectal cancer,CRC）患者中的疗效和安全性。方法：本研究为前瞻性研究设计,用PASS15 软件计算研究所需的样本量,从2017 年7 月到2018 年8 月入组标准方案治疗失败的晚期CRC患者52 例,给予阿帕替尼起始剂量750 mg或500 mg单药治疗;评估患者的客观缓解率（ORR）和疾病控制率（DCR）,随访评价患者的无进展生存期（PFS）和总生存期（OS）,并记录治疗过程中出现的不良反应。主要研究终点为PFS,次要研究终点为ORR、DCR、OS和安全性。结果：纳入研究的52 例CRC患者中45 例可以评价疗效及安全性,其均为既往接受过至少2 次系统性化疗的晚期CRC患者。疗效：完全缓解0 例、部分缓解5 例、疾病稳定30 例、疾病进展10 例,ORR为11.11%、DCR为77.78%;预后：45 例患者的中位PFS 为3.95 个月（95% CI=3.16~4.74）,中位OS为10.3 个月（95% CI=5.70~14.90）;3 级以上不良反应：手足综合征6 例（13.33%）,高血压5 例（11.11%）,蛋白尿5 例（6.67%）,转氨酶升高4 例（8.89%）,腹泻3 例（6.67%）,疲劳2 例（4.44%）,出血1例（2.22%）。结论：阿帕替尼单药治疗标准方案失败的晚期CRC患者具有潜在的临床获益,安全性事件总体可控。