Evaluation of predictive factors in patients with bladder cancer undergoing atezolizumab treatment: Case reports

This series consists of three cases. Clinical features and pathological characteristics, expression of tumor-infiltrating lymphocytes (TIL), TIL-PD-L1 expression, microsatellite instability (MSI), and programmed death-ligand (PD-L1) were evaluated for predicting response to immunotherapy in patients receiving atezolizumab for advanced bladder cancer. Tumor PDL-1 level was 80% in case 1; however, PDL-1 level was detected as 0% in other cases. TIL PDL-1 level was 5% in the first case, and 1% and 0% in the second and third cases, respectively. TIL density was higher in the first case than in the other two cases. MSI was not detected in any of the cases. With atezolizumab treatment, the radiologic response was obtained only in the first case and progression free survival (PFS) lasting 8 months was detected. In the other two cases, there was no response with atezolizumab and the disease progressed. When the clinical factors (performance status, hemoglobin level, presence of liver metastases, and response time to platinum regimen) predicting the response to the second series of treatments were evaluated, patients had a risk factor of 0, 2, and 3, respectively. The overall survival of the cases was determined as 28, 11, and 11 months, respectively. In our study, when compared with the other cases, the first case reported a higher PD-L1, higher TIL PD-L1 level, higher TIL density, and low clinical risk factors and had longer survival with atezolizumab

Research progress in atezolizumab in the treatment of lung cancer / 中国胸心血管外科临床杂志

@#In recent years, atezolizumab, a programmed death-ligand 1 (PD-L1) has shown clinical efficacies against many different solid malignancies. In late October 2016, the Food and Drug Administration (FDA) granted approval to atezolizumab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. With the development of clinical trials, the applications of atezolizumab in lung cancer treatment have gradually expanded. In this review, we summarized the current clinical status of atezolizumab in the treatment of lung cancer.

Treatment Sequencing Strategies in Lung Cancer / 中国肺癌杂志

BACKGROUND@#The advances in the lung cancer screening methods and therapeutics, together with awareness towards deleterious habits, such as smoking, is increasing the overall survival with better quality of life for the patients. However, lung cancer is still one of the most common and fatal neoplasm with a high incidence and consequently burden to public health worldwide. Thus, based on guidelines and recent phases II and III clinical trials studies, this manuscript summarizes the current treatment sequencing strategies in lung cancer.@*METHODS@#A comprehensive search of related articles was performed focused on phases II and III clinical trials studies.@*RESULTS@#The lung cancer management should take into consideration the tumor characteristics, histology, molecular pathology and be discussed in a multidisciplinary team. Lung cancer treatment options comprises surgery whenever possible, radiotherapy associate with/or chemotherapy and immunotherapy as monotherapy, or combined with chemotherapy and best palliative care.@*CONCLUSIONS@#The screening predictability in more patients, smoking reduction, early diagnosis, better disease understanding and individualized, more effective and tolerable therapeutics are related to an increasing in overall survival and quality of life. In the near future improvement of personalized therapy in precision medicine is expected, enhancing new predictive biomarkers, optimal doses and optimal treatment sequencing as well as anti-cancer vaccines development.

Current status of atezolizumab combined with bevacizumab in the treatment of hepatocellular carcinoma / 中华肝胆外科杂志

Hepatocellular carcinoma (HCC) has a hidden onset and rapid progress. Most of the patients have lost the opportunity of surgery at the onset, and the systemic treatment effect is not satisfactory. In recent years, immune checkpoint inhibitors combined with targeted therapy have brought hope to HCC patients. In particular, treatment with atezolizumab combined with bevacizumab has been recommended by many domestic and foreign guidelines as the first-line treatment for patients with unresectable HCC who have not previously received systematic treatment. In this review, the application status of atezolizumab plus bevacizumab, coping strategies for treatment failure, cost-benefit analysis and side effects were described in order to provide reference for clinical treatment.

Clinical efficacy of atezolizumab plus bevacizumab in the first-line treatment of advanced huge hepatocellular carcinoma / 中华消化外科杂志

The incidence and mortality of hepatocellular carcinoma (HCC) is very high in China, which seriously threatens human life and health. There were limited treatment options for advanced HCC in the past, and the overall survival of HCC patients was poor. In recent years, immuno-therapy and targeted therapy have been recommended as effective means for the treatment of advan-ced HCC. The authors report a case of advanced huge HCC which has achieved a maintained partial response for 6 months after the treatment of atezolizumab combined with bevacizumab. The tumor shrunk by 32.4% and 47.5% after 3 and 6 months of treatment. Besides, the alpha-fetoprotein and abnormal tumor protein value of the patient continued to decrease without any adverse reactions. The treatment is evaluated as partial response and patients has a good short-term effect.

Clinical efficacy of hepatic arterial infusion chemotherapy combined with immune plus targe-ted therapy for lung metastasis of advanced hepatocellular carcinoma / 中华消化外科杂志

Hepatocellular carcinoma (HCC) is one of the most common tumors of primary hepatic carcinoma, and one of the major causes of cancer related deaths worldwide. HCC has high incidence and mortality, with limited treatment. The prevention and treatment of HCC faces great challenges. At present, interventional therapy combined with immune plus targeted therapy has a synergistic effect and a significant effect in prolonging the survival time of patients and controlling tumors, which brings a brand-new therapeutic hope to patients with advanced HCC. The authors report a case of advanced HCC with lung metastasis who underwent hepatic arterial infusion chemotherapy combined with immune plus targeted therapy, with a result of good clinical effect on tumor controlling in a short time.

Atezolizumab-induced encephalitis in a patient with metastatic breast cancer: a case report and review of neurological adverse events associated with checkpoint inhibitors

Immune-mediated encephalitis as an adverse event due to checkpoint inhibitors is very rare. We describe herein the case of a 38-year-old woman with metastatic triple-negative breast cancer who developed seizures and somnolence twelve days after receiving the first dose of Atezolizumab. Work up ruled out all infectious etiologies, and the patient was eventually diagnosed with immune-mediated meningoencephalitis. Symptoms recovered with a high-dose of steroids, and she was found to have an excellent response on follow-up imaging, which raised the question of whether a relationship exists between the occurrence, and severity of the adverse event and the response to treatment. Only a few other cases of atezolizumab-related encephalitis have been published. Early recognition and treatment are crucial; the reason why we are describing this case along with a review of the literature and a review on all the neurological immune-related adverse events due to the different checkpoint inhibitors.

Clinical efficacy of atezolizumab plus bevacizumab for the treatment of advanced hepato-cellular carcinoma / 中华消化外科杂志

Results of the IMbrave150 clinical study showed that atezolizumab plus bevaci-zumab have better overall survival and progression-free survival than sorafenib in the treatment of hepatocellular carcinoma patients. However, hepatocellular carcinoma patients with esophageal varices were not included in the IMbrave150 clinical study mainly considering the bleeding risk of patients undergoing treatment of bevacizumab. The authors introduce the atezolizumab plus bevaci-zumab treatment of an advanced hepatocellular carcinoma patient with moderate esophageal varices. By reducing the dose of bevacizumab, the patient achieved an excellent curative effect.

Clinical efficacy of atezolizumab plus bevacizumab in the first-line treatment of advanced hepatocellular carcinoma / 中华消化外科杂志

Primary hepatic carcinoma has ranked as the sixth most commonly diagnosed cancer and the third leading cause of cancer death. China shares about 50% of new liver cancer cases, including 80% of hepatic carcinoma. Non-surgical therapy continues to make breakthroughs. The authors report a case of hepatic carcinoma with intrahepatic metastasis and tumor thrombus in the left portal vein, which has achieved continious partial response after the treatment of atezoli-zumab combined with bevacizumab, without adverse reactions such as liver and kidney function damage. The life quality of the patient was improved, showing safety and efficacy of the treatment.

Clinical efficacy of atezolizumab plus bevacizumab for first-line treatment of unresectable hepatocellular carcinoma / 中华消化外科杂志

Advanced hepatocellular carcinoma (HCC) has limited treatment options and poor prognosis. Only two tyrosine kinase inhibitors have been approved as single agents for first-line treatment over the last decade. In 2020, atezolizumab combined with bevacizumab was appro-ved for first-line treatment of advanced HCC. As the first brand-new therapy to surpass sorafenib, atezolizumab combined with bevacizumab showed good safety and life quality in patients. The authors introduced the diagnosis and treatment of a China Liver Cancer Staging Ⅲb HCC patient receiving atezolizumab combined with bevacizumab, in order to provide references for patient management.

Role of PD-1/PD-L1 signaling pathway in immune response of liver transplantation / 器官移植

Primary liver cancer (liver cancer) is one of the main indications of liver transplantation. However, postoperative recurrence of liver cancer severely affects the long-term clinical efficacy of liver transplantation. Programmed cell death protein 1 (PD-1) is an immunosuppressive molecule. Activation of PD-1/programmed cell death protein-ligand 1 (PD-L1) signaling pathway plays a pivotal role in the immune tolerance of grafts. In recent years, immune checkpoint inhibitor(ICI), such as PD-1/PD-L1 inhibitor, has become one of the effective approaches to treat advanced liver cancer, whereas ICI can be applied in liver transplant recipients is highly controversial, and the efficacy and safety remain to be studied. In this article, the expression of PD-1/PD-L1 in liver allograft tissues, the mechanism of PD-1/PD-L1 inducing transplantation immune tolerance and clinical application of PD-1/PD-L1 inhibitor in liver transplantation for liver cancer were reviewed.

Research progress on programmed death receptor 1/ ligand 1 inhibitor in immunotherapy of head and neck squamous cell carcinoma / 口腔疾病防治

@#Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor that seriously threatens human health and life. With increasing studies on the mechanism of tumor immune escape, programmed death receptor 1 (PD-1) and programmed death ligand receptor 1 (PD-L1) have been proven to be involved in tumor immune escape. The primary mechanism is that PD-1 recruits protein tyrosine phosphatase (SHP-2) to dephosphorylate downstream tyrosine kinase (SyK) and phosphatidylinositol 3-kinase (PI3K), thereby inhibiting downstream protein kinase B (AKT), extracellular regulated protein kinases (ERK) and other important signaling pathways, ultimately inhibiting T cell activation. In recent years, PD-1/PD-L1 inhibitors have become popular immunotherapies. Pembrolizumab and nivolumab have been approved for HNSCC patients by the U.S. Food and Drug Administration. Both durvalumab and atezolizumab are still in clinical trials, and published data show that both have certain safety and efficacy but still need much clinical data to support them. Meanwhile, the combination of PD-1/PD-L1 inhibitors with radiotherapy, chemotherapy and immunotherapy is still controversial in terms of clinical efficacy and adverse events, and further research is needed. However, serious immune-related adverse reactions limit the clinical application of PD-1/PD-L1 inhibitors, despite promising curative effects. Therefore, developing novel inhibitors and investigating stable and effective biomarkers and upstream and downstream signaling mechanisms are urgent issues.

Cost-utility Analysis of Atezolizumab Combined with Standard Chemotherapy Regimen in the First-line Treatment of Extensive-stage Small-cell Lung Cancer / 中国药房

OBJECTIVE：To evaluate the economics of atezolizumab combined with stardard chemotherapy regimens versus chemotherapy regimens alone as first-line treatment for extensive-stage small-cell lung cancer （ES-SCLC）from the healthcare system perspective. METHODS ：A partitioned survival model was constructed using published phase Ⅲ clinical trial data （IMpower133）and literature data to evaluate the economics of atezolizumaba combined with standard chemotherapy regimens versus chemotherapy regimens alone as first-line treatment for ES-SCLC. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the stability of the results. RESULTS ：The results of cost-utility analysis showed that the cost of atezolizumab combined with chemotherapy group was 489 598.52 yuan，with utility of 0.70 QALYs；the cost of chemotherapy alone group was 126 276.80 yuan，with utility of 0.55 QALYs；the incremental cost-utility ratio （ICUR）between the two groups was 2 361 709.05 yuan/QALY，far exceeding the willingness-to-pay （WTP）in China （3 times of GDP per capita in 2019，212 676 yuan）. One-way sensitivity analysis showed that progression-free utility value of atezolizumab combined with chemotherapy had the greatest impact on the results of cost-utility analysis ；probabilistic sensitivity analysis suggested that the atezolizumab combined with chemotherapy regimen was not economical within the WTP range of 0-500 000 yuan/QALY. CONCLUSIONS ：Atezolizumab combined with chemotherapy regimen has no cost-utility advantage versus chemotherapy alone in the first-line treatment of ES-CLC under the current economic level of China.

Checkpoint inhibitors in advanced nonsmall-cell lung cancer; a Bayesian network meta-analysis

Background: Checkpoint inhibitors (CPIs) have improved survival compared to chemotherapy alone in advanced nonsmall-cell lung cancer (NSCLC). This article aims to compare indirect evidence and rank the effect of different CPIs in this setting. Materials and Methods: In this network meta-analysis, we searched for trials comparing CPIs in advanced NSCLC. Figures for survival endpoints were extracted. In addition, a network meta-regression analysis was carried out. Results: A total of 9220 patients from 16 trials were included in the analysis. In the first-line setting, for the overall survival endpoint, the chemotherapy + Pembrolizumab combination had the highest effectivity rank probability as compared to chemotherapy (hazard ratio = 0.788, 95% credential interval = 0.728–0.855). For the second-line setting, and also for the efficacy in terms of progression-free survival, various CPIs and their combinations were ranked. Conclusion: Some degree of differences in terms of efficacy exists between different types, dosages, settings, and combinations of CPI. We quantify these differences to guide clinical practice

A Case of Pseudoprogression During Atezolizumab Therapy in Lung Adenocarcinoma / 中国肺癌杂志

Lung cancer is the most common cause of cancer-related death worldwide. There are two classes of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC represents approximately 85% of all lung cancer cases. Immune checkpoint inhibitors (ICIPs) are a class of inhibitors of programmed death-1 and programmed death-ligand 1. Preclinical studies have shown that ICIPs have shown good clinical efficacy and durable response in diverse cancers. Among them, atezolizumab (MPDL3280), an anti-PD-L1 monoclonal antibody, is being investigated as a potential therapy against solid tumors and hematologic malignancies in humans. Pseudoprogression is reported as one of the unique phenomena with immune therapeutic agents. Here we report case of a person with advanced NSCLC who developed pseudoprogression after receiving immunotherapy. We hope this case could help clinicians to make appropriate decision when assessing therapeutic effects of immunotherapy.
.

Atezolizumab in Patients with Pretreated Urothelial Cancer: a Korean Single-Center, Retrospective Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Treatment targeting immune checkpoint with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has demonstrated efficacy and tolerability in the treatment of metastatic urothelial carcinoma (mUC). We investigated the efficacy and safety of atezolizumab in mUC patients who failed platinum-based chemotherapy. MATERIALS AND METHODS: A retrospective study using the Samsung Medical Center cancer chemotherapy registry was performed on 50 consecutive patients with mUC treated with atezolizumab, regardless of their PD-L1(SP142) status, as salvage therapy after chemotherapy failure between May 2017 and June 2018. Endpoints included overall response rate (RR), progression-free survival (PFS), and safety. RESULTS: Among 50 patients, men constituted 76% and the median age was 68 years (range, 46 to 82 years). Twenty-three patients (46%) received atezolizumab as second-line therapy. PD-L1 (SP142) status IC0/1 and IC2/3 were found in 21 (42%) and 21 (42%) of patients, respectively; in eight patients (16%), PD-L1 (SP142) expression was not available. Atezolizumab was generally well tolerated, with pruritus and fatigue being the most commonly observed toxicities. As a result, partial response was noted in 20 patients (40%), with 12 (24%) stable diseases. RRwas higherin IC2/3 (62%) than in IC0/1 patients (24%, p=0.013). The median PFS was 7.4 months (95% confidence interval, 3.4 to 11.4 months). As expected, PFS also was significantly longer in IC2/3 patients than in IC0/1 (median, 12.7 vs. 2.1 months; p=0.005). PFS was not significantly influenced by age, sex, performance status, number of previous chemotherapy, site of metastases, or any of the baseline laboratory parameters. CONCLUSION: In this retrospective study, atezolizumab demonstrated clinically efficacy and tolerability in unselected mUC patients who failed platinum-based chemotherapy.