Systematic review and meta-analysis of Chinese herbal medicine as adjuvant treatment in advanced non-small cell lung cancer patients

IntroductionWhether combining Chinese herbal medicines (CHMs) and chemotherapy to treat patients with advanced non-small-cell lung cancer (NSCLC) has clinical benefits has yet to be confirmed. A meta-analysis was performed to address the efficacy of CHM in patients with advanced NSCLC.MethodsSeven databases, including PubMed, MEDLINE, Cochrane Library, Embase, CINAHL Plus with Full Text (EBSCO), WANFANG DATA and the Chinese National Knowledge Infrastructure (CNKI), were systematically searched for available literature through March10, 2020. A meta-analysis was conducted to generate combined risk ratios(RRs) with 95 % confidence intervals (CIs) for objective response rates (ORRs), disease control rates (DCRs), and 1-year overall survival (OS) rates, and a random-effects model was used to estimate the standardized mean differences (SMDs) with 95 % CI for quality or life (QOL), median survival time (mST) and progression-free survival (PFS).ResultsReports of 14 randomized controlled trials involving 1451 patients were included in the analysis. Among them, 739 patients received CHMs, and 712 patients received chemotherapy alone. The ORR (RR = 1.37, 95 % CI [1.20‐1.58], p = .000), DCR (RR = 1.13, 95 % CI [1.07‐1.21], p = 0.000), QOL (SMD = 1.47; 95 % CI [0.30–2.64]; p = 0.014), mST (SMD = 1.62; 95 % CI [1.15‐2.08];p = .000), and 1-year OS rate (RR = 1.24, 95 % CI [1.05‐1.47], p = 0.01) were higher in patients with NSCLC who received CHMs than in those who received only chemotherapy. However, the CHM group was not found to have a higher median PFS (SMD = 1.27, 95 % CI [-0.22‐2.78], p = .095) than the chemotherapy group. Publication bias for ORR and DCR was indicated by funnel plot. For the efficacy endpoint, no evidence of a lack of robustness was found, according to the sensitivity analysis. These results must be interpreted with caution due to differences in the designs of the trials and patients’ characteristics, and also due to the presence of missing data.ConclusionsOur study found that higher ORR, DCR, QOL, mST and 1-year OS rate were associated with CHM use as an adjuvant to chemotherapy. Although these results require further confirmation, CHMs apparently have potential therapeutic value for patients with advanced NSCLC.     

Pembrolizumab for the treatment of non-small cell lung cancer

ABSTRACT

Introduction: Immune checkpoint inhibitors targeting programmed death protein 1 (PD-1) receptor and its ligand, PD-L1, have recently led to significant and durable improvements in the clinical outcomes of some types of cancers including lung cancer.

Areas covered: Pembrolizumab was approved by the US FDA for the treatment of advanced or metastatic NSCLC whose disease has progressed after other treatments and with tumors that express PD-L1. In the phase I KEYNOTE-001 trial, the overall response rate (ORR) was 19.4%, the median progression-free survival (PFS) and overall survival (OS) were 3.7 months and 12.0 months for 495 unselected NSCLC patients. Strong PD-L1 expression (≥ 50%) was associated with higher ORR, longer PFS, and longer OS. The phase II/III randomized KEYNOTE-010 trial demonstrated that pembrolizumab improved OS versus docetaxel in patients with previously treated NSCLC.

Expert opinion: Pembrolizumab, demonstrated durable response and prolonged OS especially in NSCLC patients with high expression of PD-1, thereby suggests a new treatment paradigm. However, many issues remain to be explored, including the identification of other robust biomarkers that can accurately predict the immune-responsiveness of tumors. Along with the identification of predictive biomarkers, further understanding of the tumor microenvironment is necessary to improve treatment outcomes through combinations of immunotherapy or combined with other targeted therapies.     

Efficacy and safety of FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy: A systematic review and meta-analysis

ObjectiveTo undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN [irinotecan], OX [oxaliplatin]) after failure of gemcitabine-based first-line therapy in patients with pancreatic cancer.MethodsThis meta-analysis searched electronic databases, including Embase®, Medline, PubMed® and the Cochrane library, for eligible studies that reported the use of FOLFIRINOX and other drug regimens as second-line chemotherapy after failure of gemcitabine-based chemotherapy. Pooled analyses for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and grade 3/4 treatment-emergent adverse events (TRAEs) were undertaken.ResultsThe analysis included six studies with a total of 858 patients. Compared with the three other second-line regimens, FOLFIRINOX had a significantly longer PFS (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52, 0.89) and OS (HR 0.71, 95% CI 0.59, 0.86); and a significantly better ORR (HR 0.43, 95% CI 0.23, 0.80) and DCR (HR 0.71, 95% CI 0.58, 0.88). However, grade 3/4 adverse events were more frequently reported in patients administered FOLFIRINOX compared with the other three regimens.ConclusionFOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.Research Registry number: reviewregistry1300     

Traditional Chinese Medicine treatment as maintenance therapy in advanced non-small-cell lung cancer: A randomized controlled trial

ObjectivesMaintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) is an increasingly hot topic in the field of clinical NSCLC research. This study aimed to evaluate the effects of Traditional Chinese Medicine (TCM) treatment as maintenance therapy on time to progression (TTP), quality of life (QOL), overall survival (OS) and 1-year survival rate in patients with advanced NSCLC.MethodsThis study was conducted as a randomized, controlled, open-label trial. 64 non-progressive patients who responded to initial therapy were randomized 1:1 to the TCM arm (treated with herbal injection (Cinobufacini, 20 ml/d, d1–d10), herbal decoction (d1–d21) and Chinese acupoint application (d1–d21), n = 32) or to the chemotherapy arm (treated with pemetrexed (non-squamous NSCLC, 500 mg/m², d1), docetaxel (75 mg/m², d1) or gemcitabine (1250 mg/m², d1 and d8), n = 32). Each therapy cycle was 21 days. They were repeated until disease progression, unacceptable toxicity, or until the patients requested therapy discontinuation. The primary end point was TTP; the secondary end points were QOL, OS and 1-year survival rate. “Intention-to-treat” analysis included all randomized participants.ResultsTCM treatment prolonged median TTP for 0.7 months compared with chemotherapy, but it was not statistically significant (3.0 months vs. 2.3 months, P = 0.114). Median OS time for TCM treatment did not offer a significant advantage over for chemotherapy (21.5 months vs. 18.8 months, P = 0.601). 1-year survival rate of TCM treatment significantly improved than that of chemotherapy (78.1% vs. 53.1%, P = 0.035). TCM treatment can significantly improve QOL when compared to chemotherapy as assessed by EORTC QLQ-C30 and EORTC QLQ-LC13 QOL instruments.ConclusionsTCM maintenance treatment had similar effects on TTP and OS compared with maintenance chemotherapy, but it improved patients' QOL and had higher 1-year survival rate. TCM Maintenance treatment is a promising option for advanced NSCLC patients without progression following first-line chemotherapy.     

Efficacy and Safety of Programmed Cell Death 1 Inhibitor Monotherapy Versus Chemotherapy as Second-Line Treatment for Advanced Esophageal Cancer: A Meta-analysis and Systematic Review

PurposeWith programmed cell death 1 (PD-1) inhibitors approved for second-line treatment of advanced esophageal cancer, immunotherapy and chemotherapy have gradually become the main treatments for second-line treatment of patients with advanced esophageal cancer (AEC). This meta-analysis and systematic review were conducted to evaluate the efficacy and safety of PD-1 inhibitors monotherapy versus chemotherapy in second-line treatment of AEC.MethodsEligible randomized controlled trials were searched in PubMed, Embase, and the Cochrane Library and abstracts presented at the American Society of Clinical Oncology or European Society of Medical Oncology were reviewed to assess the efficacy and tolerability of PD-1/programmed cell death ligand 1 (PD-L1) inhibitors relative to chemotherapy for AEC from January 2016 to October 2020. Patients diagnosed with AEC and progressing after first-line therapy were included in this study. Hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) of objective response rate (ORR), and the odds ratios (ORs) of adverse effects (AEs) were calculated.FindingsThe study included 4 randomized controlled trials with 1683 patients. The results indicated that PD-1 inhibitors prolonged the OS (HR = 0.79; 95% CI, 0.71–0.88; P < 0.01) and improved the ORR (RR = 3.00; 95% CI, 2.36–3.82; P = 0.01) but did not improve the PFS (HR = 0.96; 95% CI, 0.76–1.20; P = 0.692) compared with chemotherapy in the second-line treatment of AEC. PD-1 inhibitors alone were associated with a lower incidence of all treatment-related AEs (OR = 0.29; 95% CI, 0.09–0.89; P = 0.03) and grade 3 to 5 treatment-related AEs (OR = 0.26; 95% CI, 0.16–0.44; P < 0.01) versus chemotherapy. PD-1 inhibitors prolonged OS mainly in the following patient groups: male, age <65 years, Eastern Cooperative Oncology Group performance status of 1, or PD-L1 tumor proportion score ≥10%. Asian patients had a longer OS than non-Asian patients (P = 0.01).ImplicationsThe available evidence indicates that the efficacy and tolerability of PD-1 inhibitors were better than chemotherapy in the second-line treatment of AEC, and the benefiting population of these patients was limited to males, those <65 years of age, those with a Eastern Cooperative Oncology Group performance status of 1, or those with a PD-L1 tumor proportion score ≥10%. Notably, Asian patients receiving immune monotherapy had longer OS than non-Asian patients.     

Pembrolizumab for the first-line treatment of non-small cell lung cancer

Introduction: Platinum-based chemotherapy had long played a role as standard therapy for the first-line treatment of advanced or recurrent non-small cell lung cancer (NSCLC). However, immune checkpoint inhibitors such as pembrolizumab, a monoclonal antibody that prevents programmed death protein 1 (PD-1) receptor, have brought a paradigm shift in this field.

Areas covered: In this article, we review the relevant literatures and ongoing trials on the first-line treatment of pembrolizumab. Especially, in two pivotal phase III trials, KEYNOTE-024 and ?189, both pembrolizumab monotherapy and combined pembrolizumab plus chemotherapy significantly prolonged overall survival (OS) compared to the existing platinum-based chemotherapy. Currently, multiple trials with combination therapy of pembrolizumab and other agents have been conducted, and further evidences are expected to be created.

Expert opinion: Immune checkpoint inhibitors that block the PD-1/PD-L1 pathway are essential drugs for advanced or recurrent NSCLC, among which pembrolizumab becomes one of the standards of care in the first-line of NSCLC. For further improvement in efficacy of pembrolizumab, it is necessary to clarify the identification of biomarkers exclusive to PD-L1 expression, predictive factors for patients who benefit most from the agent.     

希美钠在食管癌放射治疗增敏的临床应用

目的探讨希美钠在食管癌放射治疗的增敏作用及临床价值。方法回顾分析综合组（希美钠＋放疗）和单纯组（放疗）各30例。综合组采用希美钠800mg／m^2，用100ml生理盐水稀释溶解，于30min内完成静脉滴注，在60min内进行常规放疗。2～3次／周，连续用药到放疗疗程结束。用药总量6000-9000mg。单纯组只采用放射治疗。采用60Co体外照射，放疗照射剂量为6000～7000cGy／6-7周。结果近期疗效：综合组放射治疗疗效较单纯组提高40．00％，远期疗效正进一步追踪观察中。结论希美钠安全性高，毒副反应较小，对食管癌放射治疗增敏效果明显。     

长春瑞滨联合同步三维适形放疗治疗局部晚期非小细胞肺癌的临床研究

目的 评价长春瑞滨联合同步三维适形放疗在局部晚期非小细胞肺癌治疗中的近期疗效和毒副反应.方法 84例符合NSCLC诊断标准的患者随机分为两组,治疗组42例,对照组42例.两组在常规治疗的基础上,治疗组给予长春瑞滨和顺铂静脉滴注,并同步三维适形放疗,对照组给序贯化放疗治疗.结果 治疗组有效率(CR+PR)86.1%,1年生存率73.8%.对照组有效率(CR+PR)51.9%,1年生存率35.7%,两组差异有统计学意义.结论长春瑞滨与三维适形放疗同步方案能提高局部晚期非小细胞肺癌的近期疗效,且毒副反应无明显增加,值得进一步随访研究.     

长春瑞滨联合同步三维适形放疗治疗局部晚期非小细胞肺癌的临床研究

目的 评价长春瑞滨联合同步三维适形放疗在局部晚期非小细胞肺癌治疗中的近期疗效和毒副反应.方法 84例符合NSCLC诊断标准的患者随机分为两组,治疗组42例,对照组42例.两组在常规治疗的基础上,治疗组给予长春瑞滨和顺铂静脉滴注,并同步三维适形放疗,对照组给序贯化放疗治疗.结果 治疗组有效率(CR+PR)86.1%,1年生存率73.8%.对照组有效率(CR+PR)51.9%,1年生存率35.7%,两组差异有统计学意义.结论长春瑞滨与三维适形放疗同步方案能提高局部晚期非小细胞肺癌的近期疗效,且毒副反应无明显增加,值得进一步随访研究.     

长春瑞滨联合同步三维适形放疗治疗局部晚期非小细胞肺癌的临床研究

目的评价长春瑞滨联合同步三维适形放疗在局部晚期非小细胞肺癌治疗中的近期疗效和毒副反应。方法84例符合NSCLC诊断标准的患者随机分为两组,治疗组42例,对照组42例。两组在常规治疗的基础上,治疗组给予长春瑞滨和顺铂静脉滴注,并同步三维适形放疗,对照组给序贯化放疗治疗。结果治疗组有效率（CR＋Pn）86．1％,1年生存率73．8％。对照组有效率（CR＋PR）51．9％,1年生存率35．7％,两组差异有统计学意义。结论长春瑞滨与三维适形放疗同步方案能提高局部晚期非小细胞肺癌的近期疗效,且毒副反应无明显增加,值得进一步随访研究。     

Safety and efficacy of hepatic arterial infusion chemotherapy with raltitrexed and oxaliplatin post-transarterial chemoembolization for unresectable hepatocellular carcinoma

ObjectiveTo investigate the safety, efficacy, and prognostic factors of hepatic arterial infusion chemotherapy (HAIC) with raltitrexed and oxaliplatin post-transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (uHCC).MethodsThirty-seven patients with uHCC who received HAIC with raltitrexed and oxaliplatin post-TACE between June 2014 and December 2016 at our hospital were recruited. The primary endpoint was overall survival (OS), and secondary endpoint was progression-free survival (PFS). The overall response rate (ORR) was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (v4.0). The OS and prognostic factors were analyzed using the Kaplan–Meier method, log-rank test, and Cox regression models.ResultsThree (8.1%) patients achieved complete response, 17 (46.0%) patients achieved partial response, and the ORR was54.0%.The median OS and median PFS were 19.0 months and 12.0 months, respectively. The common toxicities included grade 3–4 increased aspartate aminotransferase levels (8/37,21.6%), grade 1–2 hyperbilirubinemia (75.7%, 28/37), nonspecific abdominal pain and fever, and grade 2–3 thrombocytopenia (18.9%, 7/37); no patients developed grade 3–4 neutropenia. Univariate analysis showed that the tumor diameter (≤50 mm, p = 0.028), Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.012), hepatitis B virus DNA level (p = 0.033), and derived neutrophil-to-lymphocyte ratio (dNLR; derived neutrophils/leukocytes minus neutrophils) (p = 0.003) were predictive factors for prognosis. Multivariate analysis showed that patients with BCLC stage B disease (p = 0.029) and dNLR≤2 before therapy (p = 0.004) had better prognosis.ConclusionsHAIC with raltitrexed and oxaliplatin post-TACE is a safe and efficacious therapy for patients with uHCC; in particular, those with BCLC stage B and dNLR≤2 have better prognosis.     

Real-world outcomes of patients with advanced intrahepatic cholangiocarcinoma treated with programmed cell death protein-1-targeted immunotherapy

ObjectiveThere is a lack of effective treatment to improve the prognosis of intrahepatic cholangiocarcinoma (ICC). Programmed cell death protein-1 (PD-1)-targeted immunotherapy has shown promising results in a variety of malignant tumours. However, in patients with advanced ICC, the safety and efficacy of anti-PD-1 agents remain unclear.MethodsForty-two advanced ICC patients treated with anti-PD-1 agents from August 2018 to December 2020 were retrospectively analyzed. Tumour response, overall survival (OS), progression-free survival (PFS), and time to tumour progression (TTP) were evaluated. Adverse events were also recorded.ResultsThe median duration of follow-up was 12.1 months, and the median time of treatment was 6.7 months for all patients. The median OS, median PFS, and median TTP for the whole cohort were 19.3 months, 11.6 months, and 11.6 months, respectively. The overall response rate (ORR) and disease control rate (DCR) for the whole cohort were 23.8% and 85.7%, respectively. Of the 42 evaluable individuals, two (4.8%) had hyperprogressive disease. The most common adverse events (AEs) were pain (n = 6; 14.3%), anorexia (n = 4; 9.5%), hypertension (n = 4; 9.5%), pyrexia (n = 3; 7.1%), cough (n = 3; 7.1%), and hypothyroidism (n = 3; 7.1%). The median OS of patients with albumin-bilirubin (ALBI) grade 1 was longer than that of patients with ALBI grade 2 (19.3 months vs. 14.7 months). The median PFS did not show a significant difference between ALBI grade 1 and grade 2 patients (13.6 months vs. 6.9 months).ConclusionsPD‐1‐targeted immunotherapy showed promising efficacy and safety in advanced ICC patients.

Key messages

• PD-1-targeted immunotherapy is a safe and effective treatment for advanced ICC patients.
• This study provides therapeutic strategy for advanced ICC patients.

     

PARP1单核苷酸多态性对晚期胃癌奥沙利铂化疗反应及预后的影响

目的探讨多聚腺苷二磷酸核糖聚合酶(PARP-1)单核苷酸多态性(SNP)与晚期胃癌患者化疗反应及生存时间的关联性。方法选择2016年5月至2019年12月于苏州科技城医院肿瘤内科收治的161例晚期胃癌患者,给予奥沙利铂联合替吉奥化疗,化疗前抽空腹静脉血5 ml用于提取基因组DNA。TaqMan探针法鉴别PARP1基因rs907187C/G、rs1805414T/C和rs1136410T/C多态性位点的基因型,分析各多态性对化疗客观反应率(ORR)及总生存期(OS)的影响。结果 rs907187C/G多态性与化疗敏感性存在明显关联,变异等位基因G携带者化疗ORR显著升高,CC、CG、GG基因型分别为23.2%、42.2%、53.7%(P=0.007)。杂合基因型CG化疗ORR为CC基因型的2.362倍(P=0.035);纯合变异基因型GG化疗ORR为CC基因型的3.812倍(P=0.003);CG+GG基因型化疗ORR为CC基因型的2.854倍(P=0.005)。Kaplan-Meier分析显示rs1136410T/C多态性与患者OS显著相关,变异等位基因C携带者中位OS明显延长,TT、...     

安罗替尼联合化疗治疗驱动基因阴性晚期非小细胞肺癌的疗效及对血清VEGF、bFGF、MMP-9水平的影响

目的 安罗替尼联合化疗治疗驱动基因阴性晚期非小细胞肺癌(NSCLC)的疗效及安全性.方法 前瞻性选取2018年7月至2020年6月就诊于安徽医科大学附属宿州医院的晚期NSCLC患者60例为研究对象,随机数字表法分为观察组(n=30)和对照组(n=30).观察组予以安罗替尼联合化疗治疗,对照组予以单纯化疗治疗.比较两组客...     

多靶点酪氨酸激酶抑制剂联合厄洛替尼治疗晚期非小细胞肺癌疗效和安全性的Meta分析

目的:系统评价多靶点酪氨酸激酶抑制剂联合厄洛替尼对比厄洛替尼单药治疗晚期非小细胞肺癌的疗效及安全性。方法:通过检索PubMed,Cochrane library,Web of Science,EMBASE,万方数据库,中国知网数据库和维普期刊全文数据库,收集关于多靶点酪氨酸激酶抑制剂联合厄洛替尼治疗晚期非小细胞肺癌的随机对照试验。对符合纳入标准的随机对照实验进行Meta分析,采用RevMan5.3软件进行数据处理。结果:共纳入5项随机对照研究,总计1523名患者。Meta分析表明:与厄洛替尼单药治疗相比,多靶点酪氨酸激酶抑制剂联合厄洛替尼对非小细胞肺癌患者总生存期(overall survival,OS;HR=0.86,95%CI:0.69~1.07,P>0.05)的改善差异无统计学意义,但无进展生存期(progression-free survival,PFS;HR=0.68,95%CI:0.52~0.90,P<0.05)和客观缓解率(objective response rate,ORR;RR=1.46,95%CI:1.02~2.08,P<0.05)的差异有统计学意义。联合组腹泻、皮疹、乏力、厌食、恶心呕吐和血小板减少症III,IV级不良反应的发生率高于单药组,差异有统计学意义(P<0.05);贫血、血栓、脱水、高血压和黏膜炎症III,IV级不良反应的发生率差异无统计学意义(P>0.05)。结论:与厄洛替尼单药治疗相比,多靶点酪氨酸激酶抑制剂联合厄洛替尼治疗晚期非小细胞肺癌可以提高PFS和ORR,且不良反应可耐受。但该结论需要更多的大型临床试验进一步证实。     

The advanced lung cancer inflammation index predicts outcomes of patients with non-small cell lung cancer following video-assisted thoracic surgery

ObjectiveThe advanced lung cancer inflammation index (ALI) predicts overall survival (OS) in patients with advanced lung cancer. However, few studies have tested ALI’s prognostic effect in patients with non-small cell lung cancer (NSCLC) following video-assisted thoracic surgery (VATS), especially patients at stage III. This study investigated the relationship between ALI and outcomes of patients with NSCLC following VATS.MethodsWe retrospectively examined 339 patients with NSCLC who underwent VATS at Hebei General Hospital, China. Preoperative clinical and laboratory parameters were collected and analyzed. Optimal cutoff values of potential prognostic factors, including ALI, were determined. Kaplan–Meier and Cox regression analyses were used to determine each factor’s prognostic value.ResultsThe median OS was 31 months. The optimal cutoff value for ALI was 41.20. Patients with high ALI (≥41.20) displayed increased OS (33.87 vs. 30.24 months), higher survival rates, and milder clinical characteristics. Univariate and multivariate analyses showed a significant correlation between ALI and the prognosis of patients with NSCLC, including those at stage IIIA, who underwent VATS.ConclusionsLow ALI correlated with poor outcomes in patients with NSCLC following VATS. Preoperative ALI might be a potential prognostic biomarker for patients with NSCLC following VATS, including patients at stage IIIA.     

奥沙利铂为基础的方案治疗老年晚期结直肠癌的临床观察

目的探讨奥沙利铂为基础的方案治疗老年晚期结直肠癌的疗效及安全性。方法选择经病理学确诊的46例老年晚期结直肠癌患者,均采用奥沙利铂为基础的方案化疗,其中包括FOLFOX方案18例,XELOX方案25例,另有3例为奥沙利铂联合氟尿嘧啶方案。所有患者至少完成2个周期的化疗,观察客观有效率(RR)、疾病控制率(DCR)、中位疾病进展时间(TTP)、总生存时间(OS)和化疗相关不良反应。结果 46例患者中,RR及DCR分别为39.1%和80.4%,TTP和OS分别为7.0月和24.0月。化疗相关不良反应可以耐受,Ⅰ~Ⅱ度不良反应主要包括中性粒细胞减少、血小板减少、贫血等,Ⅲ~Ⅳ度不良反应少见,主要为中性粒细胞减少和腹泻。结论奥沙利铂为基础的方案治疗老年晚期结直肠癌安全有效,值得在老年人群中进一步研究推广。     

培美曲塞治疗晚期复发性非小细胞肺癌的疗效

目的探讨培美曲塞联合铂类治疗晚期复发性非小细胞肺癌(NSCLC)的疗效以及不良反应。方法经病理学或细胞学确诊的复发性晚期NSCLC患者12例,培美曲塞500 mg/m2第1天静脉滴注,卡铂(AUC=5)第1天静脉滴注或顺铂75 mg/m2每4周重复,至少应用2个周期以上评价疗效及不良反应。结果 12例患者,完全缓解1例,部分缓解2例,稳定5例,进展4例。缓解率25%,疾病控制率66.7%。不良反应主要为轻中度的胃肠道反应和骨髓抑制。结论培美曲塞联合铂类治疗晚期复发性非小细胞肺癌疗效确切,不良反应可耐受。     

Immune checkpoint blockade as a potential therapeutic target in non-small cell lung cancer

ABSTRACT

Introduction: The recent emergence of immune checkpoint blockade therapy and the progression of immunobiology in cancer have spurred an increasing interest in the immunotherapy for advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs), designed to directly target immune inhibitory molecules, have demonstrated efficacy in the treatment of patients with advanced NSCLC.

Areas covered: In the present article, the authors summarize the mechanism, efficacy and safety of major ICIs for the treatment of advanced or metastatic NSCLC. Combinations of different ICIs or conventional therapy and/or targeted agents for NSCLC treatment in clinical trials are also updated. In addition, immune-related adverse events and the roles of inhibitory immune checkpoint molecules as potential biomarkers in the immune checkpoint blockade therapy for NSCLC are emphatically elucidated.

Expert opinion: Immunotherapies targeting the immune checkpoint pathways have shown potential to generate durable responses and improve survival for NSCLC patients. Although the toxicity profile of this immunotherapy is manageable, immune-related adverse events and drug resistance may cause therapeutic failure. Therefore, a better understanding of the mechanisms underpinning its function and the potential side effects of ICIs, as well as the identification of predictive biomarkers for patient selection are essential.     

Meta-Analysis to Assess the Efficacy and Toxicity of Docetaxel-Based Doublet Compared with Docetaxel Alone for Patients with Advanced NSCLC who Failed First-Line Treatment

PurposeThe benefit of docetaxel-based therapy in the second-line treatment of advanced non–small cell lung cancer (NSCLC) is still unclear. The goal of this meta-analysis was to assess the efficacy and toxicity of docetaxel-based doublet compared with docetaxel alone for patients with advanced NSCLC who failed to improve with first-line treatment.MethodsSeveral databases were searched, including PubMed, Embase, and the Cochrane databases. The end points were overall survival, progression-free survival (PFS), objective response rate, disease control rate, and grade 3 or 4 adverse events. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by using Review Manager version 5.2. The pooled hazard ratio (HR) or odds ratio (OR) and 95% CIs were calculated by using fixed or random effects models depending on the heterogeneity of the included trials.FindingsTwelve eligible trials involving 2680 patients were identified. The intention-to-treatment analysis found that docetaxel-based therapy significantly improved overall survival (HR, 0.89 [95% CI, 0.83–0.96]; P < 0.01), PFS (HR, 0.79 [95% CI, 0.71–0.89]; P < 0.01), objective response rate (OR, 1.73 [95% CI, 1.37–2.18; P < 0.01), and disease control rate (OR, 1.30 [95% CI, 1.09–1.55]; P < 0.01). In addition, a subgroup analysis based on type of combined drug showed that there were significant improvement in PFS and overall survival in combining docetaxel with targeted therapy. In addition, a higher incidence of grade 3 or 4 diarrhea and thrombocytopenia was observed in docetaxel-based doublet therapy.ImplicationsBased on the available evidence, docetaxel-based doublet therapy seems superior to docetaxel monotherapy as a second-line treatment for advanced NSCLC. More studies should focus on combining docetaxel with targeted therapy to identify patients who will most likely benefit from the appropriate combination targeted therapy.