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.     

Nivolumab for treating non-small cell lung cancer

Introduction: Diversion of the immune checkpoint PD-1/PD-L1 by a tumor in order to escape antitumor immunity is a hallmark of NSCLC, but offers promising new strategies. Nivolumab, a fully human monoclonal antibody, is the first PD-1 inhibitor to be approved to treat metastatic NSCLC after exciting results obtained from clinical trials.

Areas covered: This review aims to:) clarify the mechanism of action and toxicities of PD-1 inhibitors; recapitulate the results from various clinical trials that have evaluated nivolumab as a monotherapy for metastatic NSCLC; discuss the clinical and translational research axes to better use this molecule; and summarize the therapeutic combinations currently under evaluation.

Expert opinion: The contribution of this molecule to treat NSCLC is undeniable, making it a new standard of care after prior chemotherapy. Its toxicity profile is favorable but a good knowledge of new and potentially severe immune-related adverse effects such as endocrinopathy or interstitial pneumonitis is essential for its early detection and management. Better selection of patients is needed, particularly based on the discovery of predictive biomarkers, such as PD-L1 expression. Multiple associations with other checkpoint inhibitors, chemotherapy and targeted therapies are currently being studied and should pave the way toward new uses for this drug.     

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.     

PD-1/PD-L1抑制剂治疗非小细胞肺癌脑转移患者疗效的Meta分析

目的 对PD-1/PD-L1抑制剂对比化疗治疗非小细胞肺癌(non-small cell lung cancer, NSCLC)脑转移患者的疗效进行Meta分析。方法 计算机检索Pubmed、Embase、Sciencedirect、Cochrane、X-mol、中国知网、万方等数据库的文献,由2名研究者筛选文献、提取资料并对纳入研究进行偏倚风险评估,采用RevMan 5.3软件对NSCLC脑转移患者的整体生存期(overall survival, OS)、无进展生存期(progress free survival, PFS)进行Meta分析。结果 共纳入7篇随机对照试验(randomized controlled trial,RCT),包括451例NSCLC脑转移患者。Meta分析结果显示:与化疗相比,PD-1/PD-L1抑制剂能够显著提高患者的OS[HR=0.71,95%CI(0.56,0.92),P=0.008]和PFS[HR=0.53,95%CI(0.41,0.69),P<0.01];单纯化疗作为对照组,PD-1/PD-L1抑制剂联合化疗组OS[HR=0.41,95%CI(0.24,0.70),P=0.001]、PFS[HR=0.44,95%CI(0.30,0.63),P<0.01]比单药组OS[HR=0.83,95%CI(0.63,1.11),P=0.21]、PFS[HR=0.64,95%CI(0.45,0.91),P=0.01]能够更显著地降低患者的死亡风险和疾病进展风险。结论 PD-1/PD-L1抑制剂单药治疗或联合化疗对于NSCLC脑转移患者对比化疗疗效更好,其中联合化疗组优于单用组,是NSCLC脑转移患者治疗的一个优选方案。     

Pembrolizumab for the treatment of diffuse large B-cell lymphoma

ABSTRACT

Introduction: Pembrolizumab is a novel monoclonal antibody that targets the interaction between programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Pembrolizumab has shown significant clinical efficacy in Hodgkin Lymphoma (HL), but results in non Hodgkin Lymphoma (NHL) are mixed. Some NHL subtypes, which share certain genetic features with HL, such as alterations in chromosome 9p24.1 and expression of PD-L1, have shown promising responses in early phase trials.

Areas covered: In this review, we provide an overview of pembrolizumab as a compound, and present the available clinical efficacy and safety data in the treatment of diffuse large B cell lymphomas.

Expert opinion: Current early phase data suggest that single agent pembrolizumab in NHL demonstrates both efficacy and a favorable safety profile. However, it is anticipated that future treatment strategies will be biomarker-driven and incorporate pembrolizumab into combination therapies with chemotherapy and/or immunotherapy agents.     

Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity

Introduction: Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells.

Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination.

Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.     

MEDI 4736 (durvalumab) in non-small cell lung cancer

Introduction: Immune checkpoint inhibitors (ICI) are now a therapeutic option for advanced non-small cell lung cancer (NSCLC) patients. ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC. Other notable PD-L1 inhibitors under development include avelumab and durvalumab.

Areas covered: This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials, whether published or presented at international scientific conferences. Ongoing clinical trials were also reviewed.

Expert opinion: Early phase trials of durvalumab monotherapy (and in combination) have demonstrated activity in advanced NSCLC patients and it has demonstrated a good safety profile. The authors believe that durvalumab will likely play an important role in future treatment strategies for NSCLC. The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care.     

Immune checkpoint inhibition for the treatment of mesothelioma

Introduction: Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment.

Areas covered: This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords ‘mesothelioma’ combined with ‘checkpoint blockade’ OR ‘PD-L1? OR ‘PD1? OR ‘anti-CTLA4?; the search terms AND ‘clinical trial’ or AND ‘biomarker*’ were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review.

Expert Opinion: Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20–29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.     

临床、病理、MRI特征及IVIM参数联合模型预测宫颈癌程序性细胞死亡蛋白1及其配体(PD-1/PD-L1)表达

目的 基于SHAP法观察以临床、病理、MRI特征及体素内不相干运动（IVIM）成像定量参数联合模型预测宫颈癌细胞程序性死亡蛋白1（PD-1）及其配体（PD-L1）表达的价值。方法 采集63例治疗前初诊宫颈癌盆腔MRI，并对病理标本行PD-1/PD-L1免疫组织化学染色；比较PD-1表达阳性与阴性组、PD-L1表达阳性与阴性组临床、病理、MRI表现及IVIM参数（真实弥散系数D、灌注相关弥散系数D^*及灌注分数f）的差异，并以logistic回归分析筛选宫颈癌PD-1及PD-L1表达阳性的独立影响因素，建立预测宫颈癌PD-1及PD-L1表达阳性联合模型；以受试者工作特征（ROC）曲线评估模型诊断效能，以SHAP法解释其中各变量的贡献价值。结果 PD-1阳性组与阴性组、PD-L1阳性组与阴性组之间肿瘤病理分级、宫旁浸润、淋巴结转移及D值差异均有统计学意义（P均<0.05）。FIGO分期、肿瘤病理分级、宫旁浸润、淋巴结转移和D值均为宫颈癌PD-1/PD-L1表达阳性的独立影响因素（P均<0.05）；以之建立的联合模型的曲线下面积分别为0.85及0.89。根据SHAP值，联合模型中FIGO分期和肿瘤病理分级的贡献最大。结论 以宫颈癌临床、病理、MRI特征及IVIM参数D值构建的联合模型可有效预测其PD-1/PD-L1表达。     

Molecular markers related to immunosurveillance as predictive and monitoring tools in non-small cell lung cancer: recent accomplishments and future promises

ABSTRACT

Introduction: The landscape of systemic treatment options for lung cancer has rapidly evolved with the emergence of immunomodulatory agents such as neutralizing antibodies targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Another major breakthrough was the introduction of biomarkers, such as PD-L1 expression and tumor mutational burden (TMB), predicting response to immunotherapy. However, markers for monitoring treatment response are still lacking.

Areas covered: PD-L1 and TMB represent static pre-treatment evaluations. Dynamic biomarkers are required, along with static ones, to accurately predict and monitor immunotherapy response and to discriminate between responders and non-responders early in the course of treatment. The tumor immune contexture offers potential candidates that can be tested through the liquid biopsy approach, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, microRNAs (miRNAs), circular RNAs (circRNAs), RNA splice variants, and immune cell subsets.

Expert opinion: A holistic approach combining information from tissue at the time of diagnosis and serial liquid biopsy data could lead to a novel combinatorial biomarker panel with enhanced treatment monitoring potential. Incorporating information from additional parts of the tumor-host ecosystem, such as metabolic markers and the microbiome is expected to provide added value to this strategy.     

Pembrolizumab for the treatment of esophageal cancer

ABSTRACT

Introduction

Esophageal cancer (EC) is the seventh most common cancer and the sixth leading cause of cancer death. However, the prognosis of unresectable advanced or recurrent EC patients remains poor and there are few effective therapeutic agents for EC. Pembrolizumab is a monoclonal antibody that exerts anti-tumor activity by inhibiting the interaction of programmed cell death protein 1 with its ligand (PD-L1) on activated lymphocytes. Pembrolizumab monotherapy shows a significant survival benefit in metastatic or recurrent EC patients with PD-L1 CPS ≥10 as second-line treatment.     

Programmed death-1 checkpoint blockade in acute myeloid leukemia

Introduction: Immune checkpoints are regulatory pathways induced in activated T lymphocytes that regulate antigen responsiveness. These immune checkpoints are hijacked by tumors to promote dysfunction of anti-tumor effector cells and consequently of tumor escape from the host immune system.

Areas covered: Programmed death-1/programmed death ligand (PD-1/PDL-1), a checkpoint pathway, has been extensively investigated in leukemia mouse models. Expression of PD-1 on the surface of activated immune cells and of its ligands, PD-L1 and PD-L2, on leukemic blasts has been documented. Clinical trials with PD-1 inhibitors in patients with hematological malignancies are ongoing with promising clinical responses.

Expert opinion: Therapy of hematological cancers with antibodies blocking inhibitory receptors is expected to be highly clinically effective. Checkpoint inhibitory receptors and their ligands are co-expressed on hematopoietic cells found in the leukemic milieu. Several distinct immunological mechanisms are likely to be engaged by antibody-based checkpoint blockade. Co-expression of multiple inhibitory receptors on hematopoietic cells offers an opportunity for combining blocking antibodies to achieve more effective therapy. Up-regulation of receptor/ligand expression in the leukemic milieu may provide a blood marker predictive of response. Finally, chemotherapy-induced up-regulation of PD-1 on T cells after conventional leukemia therapy creates a solid rationale for application of checkpoint blockade as a follow-up therapy.     

Pidilizumab in the treatment of diffuse large B-cell lymphoma

Introduction: The programmed death-1 (PD-1) immune checkpoint pathway is an emerging target in the treatment of hematologic malignancies. Pidilizumab is an mAb that binds to PD-1 and is a safe and well-tolerated therapy. Recent data have shown clinical activity utilizing this strategy in diffuse large B-cell lymphoma (DLBCL).

Areas covered: The role of PD-1 expression in hematologic malignancies is explored. Recent clinical trials including the results of a Phase I trial in hematologic malignancies and a Phase II trial of pidilizumab following autologous hematopoietic stem-cell transplant (AHSCT) are reviewed.

Expert opinion: We review data that suggest that PD-1 is a promising target in the treatment and management of DLBCL. Changes in immune subsets following administration of pidilizumab are felt to represent on-target responses. The improvement in progression-free survival (PFS) following AHSCT supports a response to therapy. Importantly, the improvement in PFS for patients with positive FDG-PET/CT following AHSCT indicating residual disease further supports direct activity of pidilizumab in DLBCL.     

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.     

Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: A systematic review and meta-analysis

BACKGROUNDLung cancer is a major cause of death among patients, and non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers in many countries.AIMTo evaluate the clinical benefit (CB) of COX-2 inhibitors in patients with advanced NSCLC using systematic review.METHODSWe searched the six electronic databases up until December 9, 2019 for studies that examined the efficacy and safety of the addition of COX-2 inhibitors to chemotherapy for NSCLC. Overall survival (OS), progression free survival (PFS), 1-year survival rate (SR), overall response rate (ORR), CB, complete response (CR), partial response (PR), stable disease (SD), and toxicities were measured with more than one outcome as their endpoints. Fixed and random effects models were used to calculate risk estimates in a meta-analysis. Potential publication bias was calculated using Egger’s linear regression test. Data analysis was performed using R software.RESULTSThe COX-2 inhibitors combined with chemotherapy were not found to be more effective than chemotherapy alone in OS, progression free survival, 1-year SR, CB, CR, and SD. However, there was a difference in overall response rate for patients with advanced NSCLC. In a subgroup analysis, significantly increased ORR results were found for celecoxib, rofecoxib, first-line treatment, and PR. For adverse events, the increase in COX-2 inhibitor was positively correlated with the increase in grade 3 and 4 toxicity of leukopenia, thrombocytopenia, and cardiovascular events.CONCLUSIONCOX-2 inhibitor combined with chemotherapy increased the total effective rate of advanced NSCLC with the possible increased risk of blood toxicity and cardiovascular events and had no effect on survival index.     

Optimizing Patient Selection to Maximize Drug Efficacy: the Expanding Role of Pharmacogenomics in the Clinical Development of Pembrolizumab for the Treatment of Non-small Cell Lung Cancer

Pembrolizumab (MK-3475) is a potent and highly selective humanized monoclonal antibody of the immunoglobulin G4κ class directed against the immune checkpoint programmed cell death protein-1 (PD-1). Binding to PD-1 prevents its interaction with natural ligands and allows for the reactivation of the immune response against cancer cells. The list of approved indications of pembrolizumab is fast expanding, including its use as first-line treatment of metastatic non–small cell lung cancer (NSCLC), which is a complex and evolving disease. Pharmacogenomics significantly contributed to understanding this complexity, allowing for the identification of molecular biomarkers and novel pharmacologic targets. This approach has delivered more effective and less toxic drugs for advanced NSCLC. In our opinion, pharmacogenomics played a key role in the approval of pembrolizumab as frontline therapy for NSCLC with high expression of the PD-1 ligand, which occurs in ∼30% of patients. Moreover, an analysis conducted on the ongoing clinical trials sponsored by the drug's patent holder shows that the characterization and validation of additional pharmacogenomic biomarkers of response has the potential to extend the frontline clinical use of pembrolizumab in NSCLC.     

Current knowledge of Ipilimumab and its use in treating non-small cell lung cancer

Introduction: The systemic treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the identification of actionable mutations and the use of targeted agents. Unfortunately, many tumors will acquire resistance and >75% of NSCLC cases lack for an actionable gene aberration. In this setting, immunotherapy rises as effective therapeutic where immune checkpoint inhibitors have entered or are entering the market in many neoplasms, including NSCLC. Ipilimumab is a monoclonal antibody targeting CTLA-4, promoting T-cell activation and its subsequent anti-tumoral immune effect. Ipilimumab might have a very important role in NSCLC as it does in melanoma because of its synergistic effect with PD-1/PDL-1 inhibitors.

Areas covered: We summarize current results of clinical studies of ipilimumab for efficacy and safety in NSCLC and also the current knowledge about potential biomarkers for its efficacy.

Expert Opinion: Combined use of PD-1/PDL-1 and anti-CTL4 inhibitors increases the efficacy against NSCLC and it is a very promising approach not only in NSCLC but also in small cell lung cancer (SCLC) for first or second-line therapy. It’s very important to identify biomarkers that can better select the population of patients that benefit the most with these checkpoint inhibitors.     

Correlation between SACE (Subjective Angiographic Chemoembolization Endpoint) score and tumor response and its impact on survival after DEB-TACE in patients with hepatocellular carcinoma

Purpose

To asses angiographic and computed tomographic success criteria during and after transcatheter arterial drug-eluting bead chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC) and its impact on progression-free survival (PFS) and overall survival (OS).

Methods

In this retrospective single-center study, 50 patients with unresectable HCC having undergone DEB-TACE from January 2010 to July 2015 were assessed. The angiographic endpoint was classified by Subjective Angiographic Chemoembolization Endpoint (SACE) scale. Relative tumor density in arterial (D_Art) and portal venous phase (D_PV) computed tomography post- versus pre-DEB-TACE were calculated, respectively. Tumor response according to modified Response Criteria in Solid Tumors (mRECIST) was assessed. Univariate Kaplan–Meier and Cox regression analysis were carried out.

Results

SACE scores I, II, III, and IV were found in 1 (2%), 20 (40%), 15 (30%), and 14 (28%) patients, respectively. Median OS and PFS were 14.2 and 5.5 months, respectively. Death rates at 6 months, 1 year and 2 years were 24%, 38%, and 52%, respectively. SACE score during DEB-TACE significantly correlated with local and overall mRECIST results (local: p < 0.001, r = 0.49, overall: p = 0.042, r = 0.29) and inversely correlated with D_PV (p = 0.005, r = − 0.40). In univariate analysis, progressive disease (PD) according to mRECIST and increase of D_Art and D_PV were associated with significantly shorter PFS. Modified RECIST independently predicted OS (hazard ratio for complete remission vs. PD = 0.15, 95% confidence interval 0.03–0.68, p = 0.014).

Conclusions

A direct impact of SACE on PFS or OS could not be shown. However, SACE significantly correlated with local and overall mRECIST tumor response that again significantly predicted OS. We therefore postulate an indirect impact of SACE on OS. Consequently, complete embolization should be attempted.

     

Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer

ABSTRACT

Introduction: On 12 December 2014, the U.S. Food and Drug Administration (FDA) approved ramucirumab for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy.

Areas covered: This review discusses the best treatment strategy for ramucirumab, a vascular endothelial growth factor receptor-2 inhibitor for patients with advanced NSCLC.

Expert opinion: The addition of ramucirumab to docetaxel in the treatment of patients with metastatic NSCLC who have progressed on or after platinum-based chemotherapy confers a 1.4-month improvement in overall survival, with an acceptable toxicity profile. The potential impact of the approval of the programmed death receptor-1 (PD-1)-blocking antibody nivolumab or pembrolizumab on the use of ramucirumab plus docetaxel in advanced NSCLC patient population is uncertain in clinical practice. In order to improve overall outcomes for patients with advanced NSCLC, both ramucirumab plus docetaxel and the PD-1-blocking antibody should be used in any treatment line.     

Prognostic and therapeutic molecular markers in the clinical management of esophageal cancer

ABSTRACT

Introduction: Esophageal cancer is a deadly disease with high mortality. Treatment with chemotherapy, radiation, and surgery continues to leave many patients with disease progression and recurrence. Novel treatments are needed for this patient population. The development of molecular markers are important for identifying therapeutic targets, as well as prognosis.

Areas covered: This review evaluates three molecular markers in esophageal cancer: HER2, PD-L1, and MSI. The fundamentals of these markers, diagnosis, and rates of occurrence in esophageal cancer are explored. The prognostic potential of these markers is based on existing literature as well as application in clinical trials. Key trial findings pertaining to the therapeutic targets for HER2 and PD-1 as well as the role of MSI are discussed.

Expert commentary: Molecular markers are changing the practice for esophageal cancer. Therapeutic targeting for HER2 and PD-L1 have shown positive results in recent clinical trials. Trials evaluating immunotherapy as first-line agents are currently underway.