Second-line Treatment Of Advanced Non-small Cell Lung Cancer Research Articles

Response to platinum-based therapies in second-line after immunotherapy in advanced or metastatic non-small-cell lung cancer PD-L1 ≥50.

Platinum-based therapies for patients with advanced non-small-cell lung cancer (NSCLC) have classically provided overall survival (OS) rates of six to nine months and objective response rates (ORRs) of 20-30%. Whether prior immunotherapy determines a different response to platinum is currently unknown. This study aimed to analyse the current response characteristics to platinum as a second-line treatment for advanced NSCLC (PD-L1 ≥50%) after first-line immunotherapy. This retrospective study was conducted at the University Hospital of Salamanca (CAUSA) between 2016 and 2023 with patients who had advanced NSCLC (PD-L1 ≥50%) treated with second-line platinum-based therapies after immunotherapy (without mutations in EGFR, ALK or ROS1 and with Eastern Cooperative Oncology Group (ECOG) ≤1 during the first- and second-line treatments). Survival and response correlation analyses (Kaplan-Meier and log rank tests in SPSS v. 25) were performed. Subsequently, the results were compared with historical cohorts (PubMed, COCHRANE, ScienceDirect, Embase, and the clinical trial registry) who had received platinum-based therapies for advanced NSCLC. Seventeen patients were analysed (11 male and 6 female). Their median age was 67 years (interquartile range, 50-77 years). Fifteen patients (88.2%) were smokers or former smokers. The patients' main histology was adenocarcinoma (9 patients, 52.9%). All first-line treatments applied pembrolizumab (median dose: 12 cycles). Second-line platinum-based therapy achieved OS of 25 months (95% CI: 7-45 months) and progression-free survival (PFS) of 6 months (95% CI: 2.5-95 months). The ORR was 47.1% [seven patients with a partial response (PR) and one patient with a complete response (CR)]. Of the patients with PRs or CRs, 75% were treated with platinum plus pemetrexed. The one-year survival rate was 58.8%. The historical OS for first-line platinum-based doublets is 7 to 12 months, with PFS of three to five months and an ORR of 17-30%. The current response to second-line platinum-based therapies for patients with advanced NSCLC after immunotherapy appears to achieve favourable response rates and be an optimal treatment after progression to immunotherapy. Prior immunotherapy appears to enhance these patients' platinum response, though future confirmatory studies are necessary.

The Efficiency and Safety of Triple-Drug Combination of Albumin-Bound Paclitaxel, Anlotinib and PD-1/L1 Inhibitors in the 2nd or Above Line of Advanced NSCLC: A Retrospective Cohort Study.

Existing research data indicates that albumin-bound paclitaxel (nab-ptx), anlotinib, and PD-1/L1 inhibitors have individually shown efficacy in second-line and subsequent treatments for advanced non-small cell lung cancer (NSCLC). This study seeks to investigate the potential of an optimized treatment regimen in this context by combining these three drugs and evaluating both efficacy and safety outcomes. Between January 2020 and January 2022, we collected data from pre-treated advanced NSCLC patients who received a combination therapy of nab-ptx, anlotinib, and PD-1/L1 inhibitors as a second-line or later treatment. The primary endpoints for the study included the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR) and overall survival (OS), while adverse events (AEs) were also recorded. Our findings revealed that the ORR of this regimen in pretreated NSCLC patients was 35.71%, with mean PFS of 5.0 months and mean OS of 10.0 months. Further analysis suggested correlations between the efficacy of the regimen and factors such as PD-L1 expression levels, the occurrence of certain types of adverse events, and the status of NK cell activity. Additionally, the tolerable toxicity profile of this regimen indicates its potential applicability in the treatment of pretreated advanced NSCLC. Our study displayed that triple-drug combination of nab-ptx, anlotinib and PD-1/L1 inhibitors showed promising efficiency and tolerated cytotoxicity in the 2nd or above line treatment of advanced NSCLC, indicating the potential of such regimen as an important option for second-line treatment of advanced NSCLC. However, due to limitations in patient numbers, its actual clinical value awaits further research confirmation.

Immunotherapy combined with rh-endostatin improved clinical outcomes over ICIs plus chemotherapy for second-line treatment of advanced NSCLC.

e21133 Background: Despite the fact that numerous clinical and preclinical studies have demonstrated the synergistic effects of combining antiangiogenic or chemotherapy with immunotherapy, no data have been found to indicate that combination therapy is more effective and safer as second-line therapy. Methods: We retrospectively compared the effectiveness and safety of ICIs plus rh-endostatin to ICIs plus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The evaluation indicators were progression-free survival (PFS), safety profile, overall response rate (ORR), disease control rate (DCR) and 1-year survival rate. Results: The median PFS with immunotherapy plus rh-endostatin (IE) was 7.10 months (95% CI, 4.64 to 9.56) versus 5.13 months (95% CI, 4.29 to 5.97) with immunotherapy plus chemotherapy (IC) (HR, 0.56; 95%CI, 0.33 to 0.95). Treatment-related adverse events of grade 3 or 4 occurred in 7.5% of the IE group versus 25.0% of the IC group. The ORR in the IE group was 35.0% versus 20.8% in the IC group ( P = 0.137), and the DCR in the IE group was 92.5% versus 77.1% in the IC group ( P = 0.049). The 1-year survival rate for the IE group was 69.4%, which was higher than the IC group's rate of 61.4%. Conclusions: Our study demonstrates that ICIs in conjunction with endostatin therapy, demonstrate high efficacy and safety, suggesting that such a combination of therapy may be a viable treatment option for pretreated NSCLC patients in the future.

Immunotherapy combined with rh-endostatin improved clinical outcomes over immunotherapy plus chemotherapy for second-line treatment of advanced NSCLC.

Despite the fact that numerous clinical and preclinical studies have demonstrated the synergistic effects of combining antiangiogenic or chemotherapy with immunotherapy, no data have been found to indicate that combination therapy is more effective and safer as second-line therapy. We retrospectively compared the effectiveness and safety of ICIs plus rh-endostatin to ICIs plus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The evaluation indicators of this study were progression-free survival (PFS), safety profile, objective response rate (ORR), disease control rate (DCR), and 1-year overall survival (OS). The median PFS with immunotherapy plus rh-endostatin (IE) was 7.10 months (95% CI, 4.64 to 9.56) versus 5.13 months (95% CI, 4.29 to 5.97) with immunotherapy plus chemotherapy (IC) (HR, 0.56; 95%CI, 0.33 to 0.95). Treatment-related adverse events of grade 3 or 4 occurred in 7.5% of the IE group versus 25.0% of the IC group. The ORR in the IE group was 35.0% versus 20.8% in the IC group (P = 0.137), and the DCR in the IE group was 92.5% versus 77.1% in the IC group (P = 0.049). The 1-year OS rate for the IE group was 69.4%, which was higher than the 61.4% of the IC group. Our study showed that ICI therapy combined with endostatin therapy exhibits high efficacy and safety, suggesting that such a combination might be a viable treatment option for patients with pre-treated NSCLC in the future.

Short-term dynamics of circulating tumor DNA predicting efficacy of sintilimab plus docetaxel in second-line treatment of advanced NSCLC: biomarker analysis from a single-arm, phase 2 trial

ObjectiveRobust biomarker predicting efficacy of immunotherapy is limited. Circulating tumor DNA (ctDNA) sought to effectively monitor therapeutic response as well as disease progression. This study aims to investigate predictive role...

Overall Survival Prediction of Docetaxel-based Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis.

Non-small cell lung cancer (NSCLC) accounts for 75-85% of all lung cancer diagnoses. This meta-analysis sought to estimate the overall survival (OS) of NSCLC based on randomized control trials which had compared docetaxel with kinase inhibitors, antineoplastic agents, and monoclonal antibodies as second-line chemotherapy for advanced NSCLC. We selected 18 randomized control trials which used docetaxel as the standard treatment arm, while kinase inhibitors, antineoplastic agents, and monoclonal antibodies constituted the experimental arm. The methodological quality of the trial was classified according to the Modified Jadad score. Several steps were taken to reduce publication bias. A forest plot was used to graphically summarize the meta-analysis. The Hedge's g value of antineoplastic agents was 0.11 (95% CI: -0.03-0.26), while for kinase inhibitors was 0.04 (95% CI: -0.10-0.17) and monoclonal antibodies was 0.05 (95% CI: -0.02-0.13). Forest plot showed a clear though only slightly higher overall survival using docetaxel compared to those of the antineoplastic agents, kinase inhibitors, and monoclonal antibodies, due to the existence of moderate heterogeneity and lower impact. Overall, the patients in these studies who were in the standard (docetaxel) treatment arm had slightly better OS than those in the intervention treatment arm. As per the results, docetaxel was more effective in the second-line treatment of advanced NSCLC than antineoplastic agents, monoclonal antibodies, and kinase inhibitors. We infer that docetaxel-based second-line therapy for patients with advanced NSCLC is supported by our meta-analysis.

EP08.01-054 ICIs combined with Single-agent Chemotherapy in Two or More Lines Treatment for Advanced Non-Small Cell Lung Cancer

Immune checkpoint inhibitors (ICIs) monotherapy has been recommended currently by the guidelines in the second-line treatment for advanced non-small cell lung cancer (NSCLC). However, the efficacy and safety of ICIs combined with chemotherapy in second-line treatment for advanced NSCLC remain unclear.This study observed and analyzed the efficacy and safety of ICIs combined with single-agent chemotherapy in two or more lines treatment for advanced NSCLC, and explored EVs markers as medication guidance and as markers for monitoring therapeutic efficacy.

Effectiveness and Cost-Effectiveness Profile of Second-Line Treatments with Nivolumab, Pembrolizumab and Atezolizumab in Patients with Advanced Non-Small Cell Lung Cancer.

No evidence is available on the head-to-head comparison of clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) in a real-world setting. We aimed to compare the effectiveness and cost-effectiveness profile of nivolumab, pembrolizumab and atezolizumab. We used a population-based retrospective cohort study based on the healthcare utilization databases of the Lombardy Region, Italy. The study cohort included all patients with a diagnosis of lung cancer, who started a second-line treatment for advanced NSCLC with nivolumab, pembrolizumab or atezolizumab from 2015 to 30 June 2020. Overall survival and average cumulative healthcare costs were measured from the start of second-line treatment until 31 December 2020. The study cohort included 1607 patients who started a second-line treatment with ICIs, of which there were 1193 with nivolumab, 138 with pembrolizumab and 276 with atezolizumab. No differences were observed between treatment arms in terms of sex, age or comorbidities. Median OS was very similar between groups, being 8.9, 9.4 and 8.7 months, respectively, in patients treated with nivolumab, pembrolizumab and atezolizumab (p = 0.898). The adjusted hazard ratio of death of patients treated with pembrolizumab and atezolizumab, as compared to nivolumab, were 1.01 (95% CI: 0.81 to 1.25) and 1.03 (0.88 to 1.21), respectively. Healthcare cumulative costs measured in the first two years of follow-up were EUR 43,764, 46,233 and 34,116, on average, associated with nivolumab, pembrolizumab and atezolizumab, respectively. In our real-world study, atezolizumab was the ICI associated with the most favorable cost-effectiveness profile.

A single-arm phase Ib study of multiple target cytotoxic T-lymphocyte (MCTL) in combination with toripalimab as second-line therapy in advanced non-small cell lung cancer (NSCLC).

2535 Background: Anti-PD-1/ PD-L1 (programmed cell-death 1) mAb treatment has been approved in the US and in Europe as second-line treatment for advanced NSCLC because of the good tolerance and efficacy in comparison with docetaxel. Unfortunately, The objective response rate is only around 20%. Multiple Target Cytotoxic T-lymphocyte (MCTL) cells can restore the antitumor immunity to improve patient outcome. Combining MCTL cells with anti-PD-1 mAb may strengthen the results as second-line treatment in patients with advanced NSCLC. (NCT04193098). Methods: This is a single-center, open-label, phase 1b trial of combination MCTL cells with toripalimab (anti-PD-1 mAb)as second-line treatment for advanced NSCLC. Systemic therapy patients received toripalimab every 3 weeks for 12 cycles and received MCTL cells every 3 weeks for 9 cycles, then toripalimab and MCTL cells for maintenance therapy until disease progression or unacceptable toxicity. Results: From June 2019 to October 2020, 14 pts aged 43-70 years (median age 59 years) were enrolled. The squamous/non-squamous ratio was 50%/50%. 8 (57.1%) were men, 13(92.8%) were ECOG PS=0-1, 5 (35.7%) had pleural effusion, and 3 (21.4%) had bone metastases. Among 13 evaluable pts, the ORR and DCR were 38.4% and 71.4%, At the time of data cutoff, the median DOR was not reached (range 8.25m-NA), the median PFS was 399 days (range 192d-NA), and the median OS were not mature. Adverse events (AEs) occurred in 5 (38.4%), No grade≥3 AEs events occurred. Immune-related AEs were thyroid hypofunction (3, 23%) and weak (2, 15.4%). Biomarkers which correlated with efficacy and AEs are being analyzed. Conclusions: Multiple Target Cytotoxic T-lymphocyte (MCTL) in combination with toripalimab as second-line treatment for advanced NSCLC because of the well tolerated and encouraging efficacy. Further studies are warranted to confirm these results. Research Sponsor: Tianjin Medical University Cancer Institute and Hospital. Clinical trial information: NCT04193098.

CAR-T Immunotherapy and Non-small Cell Lung Cancer: Bottleneck and Dawn

伴随人们对威胁人类健康的非小细胞肺癌（non-small cell lung cancer, NSCLC）更深入的病理生理和发病机制的全新理解，NSCLC治疗已进入一个新时代。从传统以手术、放化疗为基础的治疗过渡到以个体化精准化的靶向治疗和安全性及效能更高的免疫治疗。免疫检查点抑制剂疗法已经被批准为晚期NSCLC一线或者二线的治疗方案，并且取得非同凡响的临床效果。然而，其他类型的免疫治疗在NSCLC中鲜有探索。嵌合抗原受体修饰T细胞（chimeric antigen receptor modified T cells, CAR-T cells）在治疗几种血液系统恶性肿瘤方面表现不俗。然而，其在治疗包括NSCLC在内的实体瘤患者方面却不甚理想。本综述旨在系统阐释CAR-T在NSCLC治疗中的最新进展，主要包括：CAR分子靶标选择、CAR-T功能增强及相关毒性的管理以及CAR-T治疗NSCLC的困境及展望，旨在为NSCLC的免疫治疗开拓新的视角和独特的思路，为肿瘤免疫治疗大厦添砖加瓦。

PCN79 AN ECONOMIC EVALUATION OF NIVOLUMAB COMPARED WITH DOCETAXEL AS THE SECOND-LINE TREATMENT FOR PATIENTS WITH ADVANCED NSCLC IN CHINA USING MARKOV MODEL AND PARTITIONED SURVIVAL MODEL

This study aimed to evaluate the cost-effectiveness of nivolumab versus docetaxel as the second-line treatment for patients with advanced non-small cell lung cancer (NSCLC). A three-state Markov model and a partitioned survival (PS) model were conducted from the healthcare system perspective to calculate the lifetime incremental cost-effectiveness ratio (ICER) of nivolumab compared with docetaxel. Clinical data came from the landmark RCT Checkmate 078, which was mainly based on the Chinese population. The survival curves of nivolumab and docetaxel were reconstructed independently, and different parametric survival distributions were further used for fitting and extrapolating the curves. The optimal distributions were determined by the AIC/BIC. Cost inputs were derived from government documents of 10 representative provinces in China, the published literature and expert opinions to reflect the real-world situation. Utilities were derived from published literature. AEs were also considered in costs and utilities. Costs and outcomes were discounted at the annual rate of 5%. Sensitivity analyses and scenario analyses were also performed. In base-case analysis, the Markov model showed that compared to docetaxel, nivolumab had an ICER of $81,379/QALY. In the sensitivity analysis, one-way sensitivity analysis showed that the weight of the cohort, the cost of nivolumab and the health state utilities had a significant impact on the ICER. Monte-Carlo Simulation showed that the base-case result was robust, with more than 99% of scattered points fell above the WTP threshold in China ($30,297/QALY) on the cost-effectiveness plane. PS model showed that the ICER equaled to $81,615/QALY, which was in line with the results of the Markov model. The incremental QALY (0.46) was consistent with the Western population-based studies (0.16-0.66). Although nivolumab is recommended by many guidelines, currently it’s not cost-effectiveness as the second-line treatment of advanced NSCLC in China compared with docetaxel.

Cost-effectiveness of Osimertinib as a Second-line Treatment in Patients With EGFR-mutated Advanced Non–Small Cell Lung Cancer in China

PurposeTo assess the cost-effectiveness of osimertinib used as a second-line treatment after failure of epidermal growth factor receptor tyrosine kinase inhibitor therapy for advanced non–small cell lung cancer (NSCLC) in China. MethodsFrom the perspective of China's health care system, a Markov model was used for estimating the costs and health outcomes of osimertinib and 4 platinum-based chemotherapies, including pemetrexed + platinum (PP), gemcitabine + platinum (GP), docetaxel + platinum (DP), and paclitaxel + platinum (TP). Two scenarios were considered, one in all confirmed patients with T790M-positive disease (scenario 1) and the other in all patients whose disease progressed after epidermal growth factor receptor tyrosine kinase inhibitor therapy, which consisted of patients with T790M-positive or T790M-negative NSCLC (scenario 2). Clinical data for transition probabilities and treatment effects were obtained from published clinical trials. Health care resource utilization and costs were derived from local administrative databases and published literature. Deterministic and probabilistic sensitivity analyses were conducted to assess the uncertainty of the results. FindingsIn the base-case analysis, compared with the 4 platinum-based chemotherapies, osimertinib yielded an additional 0.671 to 0.846 quality-adjusted life-year (QALY), with incremental costs of 15,943 to 20,299 USD in scenario 1, and an additional 0.376 to 0.808 QALY with incremental costs of 9710 to 15,407 USD in scenario 2. In the probabilistic sensitivity analysis, the probabilities that osimertinib would be cost-effective were 57.7% in scenario 1 and 58.4% in scenario 2 if the willingness-to-pay threshold were 30,000 USD/QALY, and probabilities would be more than 75 % in both scenarios if the willingness-to-pay threshold were 50,000 USD/QALY. ImplicationsOsimertinib is likely to be cost-effective when used as a second-line treatment of advanced NSCLC in China based on the latest reimbursement price of osimertinib through National Reimbursement Drug List negotiation.

Progress in Clinical Researches of PD-1/PD-L1 Checkpoint Inhibitor for Non-small Cell Lung Cancer

非小细胞肺癌（non-small cell lung cancer, NSCLC）是肺癌最常见的病理类型。近年来，免疫治疗迅速发展，免疫检查点抑制剂尤其是程序性死亡因子-1（programmed death-1, PD-1）/程序性死亡因子配体-1（programmed death-ligand 1, PD-L1）抑制剂已在NSCLC的治疗中取得突破性进展，改变了NSCLC治疗的格局。以PD-1/PD-L1为靶点的免疫检查点抑制剂无论在晚期NSCLC的一线和二线治疗，局部晚期NSCLC的辅助治疗，还是早期NSCLC的新辅助治疗中均为患者带来获益，在NSCLC的综合治疗中显示出重要地位。本文针对以PD-1/PD-L1为靶点的免疫检查点抑制剂在NSCLC中的临床研究进展展开综述。

Progress of immunotherapy in the first-line treatment of advanced non-small cell lung cancer

In recent years, immunotherapy has gradually become a new treatment method of neoplasms, and the patients with solid tumors can benefit from immunotherapy. Immunotherapy has also been used in the treatment of non-small cell lung cancer (NSCLC), which shows a remarkable effect. At present, programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have achieved obvious effects in the treatment of NSCLC. With the continuous study of clinical trials, immunosuppressants have obtained indications in the first-line and second-line treatment of advanced NSCLC. This new treatment changes the treatment mode of lung cancer, and it also brings challenges for the treatment of efficacy evaluation and treatment-related adverse reactions of the tumors. This review summarizes the progress of immunotherapy as the first-line treatment of patients with advanced NSCLC. Key words: Carcinoma, non-small-cell lung; Immunotherapy; Programmed death 1; Programmed death ligand 1

Pemetrexed versus Gefitinib as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials

Abstract Objective To investigate the clinical efficacy and toxicity of Pemetrexed versus Gefitinib as second-line treatment for advanced non-small cell lung cancer (NSCLC). Methods By systematically searching the electronic databases of Pubmed, CENTRAL, Cochrane, EMBASE, ASCO, and CBM, open published randomized clinical trials (RCTs) relevant to clinical efficacy and toxicity of Pemetrexed versus Gefitinib as second-line treatment of advanced NSCLC were included in the meta-analysis. Data of objective response rate (ORR) and drug related toxicity were extracted from the original publications and pooled by random or fixed effect method. Results Fourteen clinical trials related to Pemetrexed versus Gefitinib as second-line treatment for advanced NSCLC fulfilled the inclusion criteria and were included in the meta-analysis. The pooled results show that the ORR (RR=0.81, 95% CI:0.56–1.16, p=0.25) and DCR (RR=1.11, 95% CI:0.94–1.31, p=0.24) were not statistical different for Pemetrexed versus Gefitinib as second-line treatment of advanced NSCLC. However, the pooled data demonstrated the risk of developing skin rash (RR=0.10, 95% CI:0.03–0.30, p=0.00) and diarrhea (RR=0.31, 95% CI:0.15–0.67, p=0.003) in patients with Pemetrexed was significantly lower than that of Gefitinib through random effect model analysis, but the incidence of neutropenia in Pemetrexed group was significantly higher than that of Gefitinib with statistical difference (RR=7.62, 95% CI:3.71–15.66, p=0.00). Conclusion Pemetrexed was not inferior as second-line treatment for advanced NSCLC compared to Gefitinib for tumor response. However, Pemetrexed had higher incidence of neutropenia but lower risk of developing skin rash and diarrhea.

First-Line Treatment in EGFR Mutant Non-Small Cell Lung Cancer: Is There a Best Option?

First generation or second generation EGFR tyrosine kinase inhibitors are currently the standard of care for the first-line management of non-small cell lung cancer (NSCLC) patients with activating mutations within the kinase domain of the epidermal growth factor receptor gene (1, 2). Resistance to targeted therapy can develop after 9–11 months (3–8). Third generation inhibitors were developed to target the EGFR T790M clone, which is the most common dominant second site resistance mutation after first or second generation inhibitors. Osimertinib received full FDA approval for the second-line treatment of advanced NSCLC based on a phase III study comparing the compound to chemotherapy. Recent data demonstrates an important impact for osimertinib in the front-line space based on results comparing the compound to first-generation erlotinib or gefitinib therapy.

Atezolizumab: feasible second-line therapy for patients with non-small cell lung cancer? A review of efficacy, safety and place in therapy.

Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC. We performed a literature search of PubMed, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference on Lung Cancer meetings. Atezolizumab showed a good tolerance profile and efficacy in comparison with docetaxel for second-line treatment of advanced NSCLC. Potential predictive biomarkers also have to be assessed.

The Role of the Antiangiogenetic Ramucirumab in the Treatment of Advanced Non Small Cell Lung Cancer.

Angiogenesis is one of the most important phenomena sustaining tumor development and metastatization, including for non small cell lung cancer (NSCLC). A dominant role in angiogenesis is played by the vascular endothelial growth factor (VEGF) and its signaling pathway. Ramucirumab, is a fully human immunoglobulin G1 monoclonal antibody that binds to the extracellular domain of the VEGF receptor-2 (VEGFR-2) with high specificity and affinity blocking the interaction of VEGFR-2 and VEGF ligands, thus inhibiting their signaling pathways and the consequential endothelial proliferation and migration. A recent phase III randomized trial named REVEL, demonstrated the efficacy of ramucirumab in combination with docetaxel as second line treatment of advanced NSCLC, leading to its FDA and EMA approval in this clinical setting. In the REVEL trial advanced NSCLC patients whose disease had progressed after first line platinum-based chemotherapy, were administered ramucirumab plus docetaxel or placebo plus docetaxel. More than 1,250 patients were treated and patients randomized to the treatment with ramucirumab plus docetaxel showed a significant longer median overall survival compared to those randomized to chemotherapy only. Ramucirumab is the first antiangiogenetic agent approved in the treatment both of squamous and non squamous NSCLC. In fact, it is not associated with increased risk of respiratory bleeding in the squamous histology, and also has demonstrated efficacy in both histology types. The role of ramucirumab, already cleared in the second-line treatment of advanced NSCLC, needs to be clarified further and is currently being explored also in the first-line treatment of advanced NSCLC.

New targeted treatments for non-small-cell lung cancer - role of nivolumab.

Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017) and non-squamous NSCLC (CheckMate 057). In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively). Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors.

The influence of autologous cytokine-induced killer cell treatment on the objective efficacy and safety of gefitinib in advanced non-small cell lung cancer

Abstract Objective The aim of the study was to observe the influence of autologous cytokine-induced killer cell (CIK) treatment on the objective efficacy and safety of gefitinib in advanced non-small cell lung cancer (NSCLC). Methods Sixty-six patients with NSCLC received gefitinib as second-line treatment. They were randomly divided into 2 groups, and informed consent forms were signed before grouping. Gefitinib was administrated to the control group, and autologous CIK treatment was added to the observation group. The objective treatment and adverse reactions were evaluated in both groups. Results The objective response rate (ORR) and the disease control rate (DCR) of the observation group were slightly higher than those of the control group, although no statistical differences were found between the 2 groups (P > 0.05). The incidences of diarrhea, fatigue, anorexia, oral ulcers, and myelosuppression in the observation group were much lower than those in the control group (P < 0.05). However, there were no statistical differences between the incidences of skin rash, and liver and kidney toxicities (P > 0.05). Conclusion Autologous CIK in combination with gefitinib is effective as second-line treatment for advanced NSCLC, and can significantly reduce adverse reactions and improve the objective efficacy.