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.     

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.     

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.     

Anti-programmed cell death-1 and anti-programmed cell death ligand-1 immune-related liver diseases: from clinical pivotal studies to real-life experience

ABSTRACT

Introduction

Monoclonal antibodies directed against programmed cell death-1 (anti-PD-1) and its ligand (anti-PD-L1) showed a significant efficacy among different immunogenic metastatic tumors such as melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC). Between immune-related adverse events (irAEs) dependent on immune checkpoint inhibitors (ICPIs), immune-related liver diseases are uncommon and a definitive diagnosis is not always feasible.     

Toripalimab in an advanced non-small cell lung cancer patient with poor general condition after multiline treatment: a case report

Several clinical trials have proven that immunotherapy can improve survival and benefit non-small cell lung cancer (NSCLC) patients. In patients who progress after chemotherapy, immune checkpoint inhibitor (ICI) monotherapy can prolong overall survival compared with patients receiving single-agent chemotherapy. A 61-year-old man diagnosed with advanced NSCLC and without driver variants received first-line chemotherapy but experienced recurrence. During subsequent treatment, the disease progressed rapidly, and his general condition deteriorated; therefore, toripalimab monotherapy was initiated. Surprisingly, he responded well, and symptoms were relieved after several treatment cycles despite pseudoprogression, shown in chest images. For driver gene-negative NSCLC patients who progress after chemotherapy and who develop poor performance status (PS), ICIs are an option to alleviate symptoms and improve survival. Furthermore, immunotherapy in patients with pseudoprogression may also provide a survival benefit.     

靶向程序性死亡分子1抑制剂治疗晚期鳞状非小细胞肺癌2例并文献复习

目的 靶向程序性死亡分子1（programmed cell death ligand 1,PD 1）通路的肿瘤免疫治疗在多种类型肿瘤中取得了卓越的临床疗效,包括非小细胞肺癌（non small cell lung carcinoma,NSCLC）。本研究关注2种靶向结合PD 1受体的单克隆抗体Pembrolizumab和Nivolumab一线治疗在我国晚期NSCLC患者中的疗效。方法 2例未接受过任何治疗的确诊为晚期鳞状NSCLC患者,患者甲给予Pembrolizumab 100mg/3w、患者乙给予Nivolumab 2 mg/（kg·2 w）,均静脉注射,定期评估疗效。结果 经2周期治疗后,2例患者肺部肿瘤均达部分缓解（partial response,PR）,呼吸系统症状及炎症好转;患者甲最终因肺癌脑转移于免疫治疗第3周期后死亡。患者乙治疗期间肺部原发病灶逐渐缩小,疗效评价PR;拟行第4周期治疗时发现脑部多发转移瘤,拟行第5周期时脑部多发转移瘤较前略有增大,疗效评价稳定（stable disease,SD）,迄今仍在维持治疗。治疗期间,2例患者肿瘤标志物CA125均显著下降。治疗期间未观察到不良反应。结论 初步研究显示PD 1抑制剂治疗晚期NSCLC原发病灶疗效显著,安全性好,血清CA125浓度可作为一个评价疗效的观察指标。但PD 1抑制剂对控制脑部转移灶的疗效需要进一步研究。由于本研究入组人数较少,此结论尚需得到进一步的论证。     

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 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.     

Dynamic changes in the radiologic manifestation of a recurrent checkpoint inhibitor related pneumonitis in a non-small cell lung cancer patient: A case report

BACKGROUNDAs immune checkpoint inhibitors (ICIs) have become widely used in lung cancer treatment, immune-related adverse events (irAEs) warrant sufficient attention. Checkpoint inhibitor-related pneumonitis (CIP) is one of the most concerning adverse events as it is uncommon but life threatening.CASE SUMMARYThe patient whose case is reported here experienced three episodes of CIP in a span of 4 mon. Interestingly, the three episodes of CIP involved different regions of the lung separately. Taking these pneumonitis areas together makes nearly a whole lung area.CONCLUSIONThis case showed that recurrent CIPs may occur repeatedly until the whole lung is involved, suggesting that the follow-up period of CIP should be long enough, and the rechallenge of ICI should be done with due caution.