scholarly journals Incidence of Infections and Predictors of Mortality during Checkpoint Inhibitors Immunotherapy in Patients with Advanced Lung Cancer: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Davide Fiore Bavaro ◽  
Pamela Pizzutilo ◽  
Annamaria Catino ◽  
Fabio Signorile ◽  
Francesco Pesola ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cox Regression ◽  
Opportunistic Infections ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Lung Cancer ◽  
Predictors Of Mortality ◽  
Concurrent Infections ◽  
Tract Infections

Abstract Background Immune checkpoint inhibitors (ICIs) have revolutionized non–small cell lung cancer (NSCLC) treatment, significantly increasing overall survival of patients. However, the incidence of concurrent infections and their management is still debated. Methods From August 2015 to October 2019, all consecutive patients with NSCLC who received Nivolumab or Pembrolizumab as first- or second-line therapy have been retrospectively evaluated. At the time of analysis all patients were dead. Clinical characteristics of patients, type of infections and predictors of mortality were analyzed. Results A total of 118 patients, 74 in the Nivolumab group and 44 in the Pembrolizumab group, were identified. At least one infection was recorded in 22% of the Nivolumab-group vs 27% of the Pembrolizumab-group (p=.178). In both groups, the main infection was a pneumonia, followed by skin and soft tissue infections, urinary tract infections and gastroenteritis. Crude mortality for first infection was 10.7%, followed by 25% and 40% for second and third recurrence, respectively (p for trend=.146). No opportunistic infections were recorded. Notably, by Cox-regression model, the independent predictor of mortality was a higher Eastern-Cooperative-Oncology-Group (ECOG) performance status at baseline (p<.001), while the multidisciplinary diagnosis and treatment of concurrent infections was associated with a reduced probability of mortality (aHR= 0.50; 95%CI=0.30 – 0.83, p<.001). Conclusions In patients with NSCLC treated with ICIs, multidisciplinary management of concurrent infections may reduce the risk of mortality. Further studies to investigate risk factors for infections, as well as appropriate management strategies and preventive measures in this setting are warranted.

scholarly journals Efficacy of Immune Checkpoint Inhibitors for Lung Cancer According to Patient Age and Eastern Cooperative Oncology Group Performance Status: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Xue-lin Zou ◽  
Wei-yong Chen ◽  
Guang-yan Zhang ◽  
Hua Ke ◽  
Jiao Yuan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Age Groups ◽  
Oncology Group ◽  
Patient Age ◽  
Ecog Ps

Abstract Background For treatment of advanced lung cancer, immune checkpoint inhibitors (ICIs) + chemotherapy or the combination of dual ICIs has become the standard first-line treatment in recent years. Considering the differences among patients’ immune systems, the response to ICIs may vary. Therefore, we aimed to evaluate the predictive implications of patient age and Eastern Cooperative Oncology Group (ECOG) performance status (PS) for the efficacy of ICIs for the treatment of lung cancer. Methods We searched the PubMed, Cochrane Library, Web of Science, and EMBASE databases for articles published between January 2010 and September 2020 that compared overall (OS) and progression-free survival (PFS) rates between patients with lung carcinoma who were administered ICIs and control treatments. Results Twenty-four trials including 15,584 patients were selected. ICIs significantly improved the OS rates in patients aged < 65 (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65–0.82) and ≥ 65 (0.75 [0.70–0.82]) years, with an age cut-off of 65 years; patients aged < 65 (0.83 [0.72–0.95]) years, when age was classified as < 65, 65–74, and ≥ 75 years; and patients with an ECOG PS score of 0 (0.77 [0.69–0.86]) and 1 (0.78 [0.72–0.85]). However, the differences between the two age groups (p = 0.69), the three age groups (p = 0.43), and the ECOG PS groups (p = 0.82) were not insignificant. Significant advantages of ICIs in terms of PFS rates were found in patients aged < 65 (0.64 [0.52–0.79]) and ≥ 65 (0.73 [0.64–0.84]) years and in those with an ECOG PS score of 0 (0.63 [0.49–0.82]) and 1 (0.66 [0.59–0.75]). No significant difference was observed between the age (p = 0.35) and ECOG PS groups (p = 0.89). Conclusions Younger patients benefited more from ICI administration; however, lung cancer treatment cannot be decided based on age. Patients with different ECOG PS could benefit from ICIs, but data on patients with an ECOG PS score of ≥ 2 are lacking. In future studies, more patients with poor ECOG PS scores should be included.

scholarly journals Expanded human NK cells from lung cancer patients sensitize patients’ PDL1−negative tumors to PD1-blockade therapy

2021 ◽  
Vol 9 (1) ◽  
pp. e001933
Author(s):  
Sophie M Poznanski ◽  
Tyrah M Ritchie ◽  
Isabella Y Fan ◽  
Abdullah El-Sayes ◽  
Ana L Portillo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Combined Treatment ◽  
Death Receptor ◽  
High Rate ◽  
Advanced Lung Cancer ◽  
Pd1 Blockade

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1−blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients’ tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1− patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.

scholarly journals Myosteatosis as a novel prognostic biomarker after radical cystectomy for bladder cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shimpei Yamashita ◽  
Yuya Iwahashi ◽  
Haruka Miyai ◽  
Takashi Iguchi ◽  
Hiroyuki Koike ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Cox Regression ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Psoas Muscle ◽  
Hounsfield Units ◽  
Computed Tomography Images ◽  
Psoas Muscles

AbstractThis study aims to evaluate the influence of myosteatosis on survival of patients after radical cystectomy (RC) for bladder cancer. We retrospectively identified 230 patients who underwent RC for bladder cancer at our three institutions between 2009 and 2018. Digitized free-hand outlines of the left and right psoas muscles were made on axial non-contrast computed tomography images at level L3. To assess myosteatosis, average total psoas density (ATPD) in Hounsfield Units (HU) was also calculated as an average of bilateral psoas muscle density. We compared cancer-specific survival (CSS) between high ATPD and low ATPD groups and performed cox regression hazard analyses to identify the predictors of CSS. Median ATPD was 44 HU (quartile: 39–47 Hounsfield Units). Two-year CSS rate in overall patients was 76.6%. Patients with low ATPD (< 44 HU) had significantly lower CSS rate (P = 0.01) than patients with high ATPD (≥ 44 HU). According to multivariate analysis, significant independent predictors of poor CSS were: Eastern Cooperative Oncology Group performance status ≥ 1 (P = 0.03), decreasing ATPD (P = 0.03), non-urothelial carcinoma (P = 0.01), pT ≥ 3 (P < 0.01), and pN positive (P < 0.01). In conclusion, myosteatosis (low ATPD) could be a novel predictor of prognosis after RC for bladder cancer.

scholarly journals Effectiveness and Safety of Immune Checkpoint Inhibitors for Patients with Advanced Non Small-Cell Lung Cancer in Real-World: Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1388
Author(s):  
Manlio Mencoboni ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
Paola Taveggia ◽  
Alessia Cavo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Small Cell Lung ◽  
Eligibility Criteria

Immunotherapy based on anti PD-1/PD-L1 inhibitors is the new standard of advanced non-small cell lung cancers. Pembrolizumab, nivolumab and atezolizumab are used in clinical practice. The strict eligibility criteria of clinical trials do not allow researchers to fully represent treatment effects in the patients that will ultimately use these drugs. We performed a systematic review and a meta-analysis to evaluate the effectiveness and safety of these drugs, and more generally of ICIs, as second-line therapy in NSCLC patients in real world practice. MEDLINE, PubMed, Scopus and Web of Science were searched to include original studies published between January 2015 and April 2020. A total of 32 studies was included in the meta-analysis. The overall radiological response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and overall survival (OS) were 21%, 52%, 3.35 months and 9.98 months, respectively. The results did not change when analysis was adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) and age. A unitary increase in the percent of patients with liver and CNS metastases reduced the occurrence of DCR by 7% (p < 0.001) and the median PFS by 2% (p = 0.010), respectively. The meta-analysis showed that the efficacy and safety of immunotherapy in everyday practice is comparable to that in clinical trials.

scholarly journals Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhenyu Ding ◽  
Qing Li ◽  
Rui Zhang ◽  
Li Xie ◽  
Yang Shu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dendritic Cell ◽  
Cancer Treatment ◽  
Checkpoint Inhibitors ◽  
Rapid Development ◽  
Therapeutic Modality ◽  
Advanced Lung Cancer ◽  
Cell Vaccine ◽  
Lung Cancer Treatment ◽  
Dc Vaccine

AbstractNeoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3–14 doses/person). In total, 12–30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1–2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.

scholarly journals Astragalus Polysaccharide Injection (PG2) Normalizes the Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Lung Cancer Receiving Immunotherapy

2021 ◽  
Vol 20 ◽  
pp. 153473542199525
Author(s):  
Shih Ming Tsao ◽  
Tz Chin Wu ◽  
JiZhen Chen ◽  
Feichi Chang ◽  
Thomos Tsao
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Treatment Initiation ◽  
Checkpoint Inhibitors ◽  
Neutrophil To Lymphocyte Ratio ◽  
Advanced Lung Cancer ◽  
Control Group ◽  
Lymphocyte Ratio ◽  
Astragalus Polysaccharide

Objectives: The neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in patients with cancer receiving immunotherapy. Recent studies have shown that a high NLR was associated with a poor response and decreased survival. However, there is no intervention to reverse abnormally high NLR and improve clinical outcomes. Astragalus polysaccharide injection (PG2) is an immunomodulatory therapy for cancer-related fatigue. This study aimed to examine whether PG2 might normalize the NLR and affect the overall survival of patients with lung cancer treated with immunotherapy. Materials and Methods: We retrospectively examined the medical records of patients with lung cancer treated with immune checkpoint inhibitors (ICIs) between October 1, 2015 and November 30, 2019. All patients received ICI combination chemotherapies, and some similarly received PG2 (Control vs PG2). The NLR was assessed before treatment and 6 weeks after ICI initiation, and the survival data was collected at least 4 years after treatment initiation for the first enrolled patient. Results: Fifty-three patients were included. Six weeks after ICI initiation, 91.3% of the patients in the PG2 group exhibited a predefined “Decrease or no change” in the NLR, which was 28% higher than that in the Control group (63.3%) ( P = .028). The NLR significantly decreased by 31.60% from baseline in the PG2 group ( P = .012), whereas it increased by 5.80% in the Control group ( P = .572). Six weeks after ICI treatment initiation, both groups had a median NLR of 3.73, and the overall survival was also similar (PG2 vs Control, 26.1 months vs 25.4 months, respectively); however, the PG2 group had a higher median baseline NLR than the Control group (PG2 vs Control, 4.51 vs 2.81, respectively). Conclusion: This study demonstrated that PG2 could normalize the NLR in patients with lung cancer receiving ICI combination treatments.

Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

2021 ◽  
pp. 1-4
Author(s):  
Tanzeel Janjua ◽  
Fei Sun ◽  
Katy Clarke ◽  
Pete Dickinson ◽  
Kevin Franks ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Early Stage ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Lung Cancer ◽  
Cox Regression Analysis

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

scholarly journals Association of Brain Metastases With Immune Checkpoint Inhibitors Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanning Wang ◽  
Qianning Zhang ◽  
Chuansheng Chen ◽  
Yuxuan Hu ◽  
Liyun Miao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Hazard Ratios

BackgroundIn pivotal immunotherapy trials, the efficacy of immune checkpoint inhibitors as treatments for lung cancer patients with brain metastases remains controversial. The aim of this study was to assess the relative efficacy of immunotherapy versus standard systemic therapy in advanced lung cancer patients with and without brain metastases.MethodsSystematic searches of PubMed, Embase, Cochrane database, and conference proceedings up to Aug 6, 2020 without year and language restrictions. The main outcomes were the overall survival in patients with and without brain metastases measured by hazard ratios, and the difference in efficacy between patients with and without brain metastases was measured by ratio of hazard ratios.ResultsNine eligible randomized controlled trials involving 6241 patients (682 [11%] with brain metastases and 5559 [89%] without brain metastases) were included in the analysis. A survival benefit of immunotherapy was observed for both patients with brain metastases (HR, 0.75; 95%CI, 0.53-0.97; P = .026) and patients without brain metastases (HR, 0.75; 95%CI, 0.67-0.83; P &lt;.001). However, patients without brain metastases benefit more from immunotherapy than patients with brain metastases (HR, 1.37; 95%CI, 1.15-1.63; P = .001). Additionally, subgroup analyses indicated that tumor type affect the efficacy of immunotherapy in patients with brain metastases (HR, 1.04 vs 1.54; interaction, P = .041).ConclusionsImmunotherapy can significantly improve overall survival for advanced lung cancer patients with asymptomatic brain metastases, especially in patients with non-small-cell lung cancer, but the magnitude of benefit is brain metastases dependent.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020206597.

scholarly journals Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectal cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. e000375 ◽  
Author(s):  
Jean-David Fumet ◽  
Nicolas Isambert ◽  
Alice Hervieu ◽  
Sylvie Zanetta ◽  
Jean-Florian Guion ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Performance Status ◽  
Human Monoclonal Antibody ◽  
Eastern Cooperative Oncology Group ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Mutational Status

Background5-Fluorouracil plus irinotecan or oxaliplatin alone or in association with target therapy are standard first-line therapy for metastatic colorectal cancer (mCRC). Checkpoint inhibitors targeting PD-1/PD-L1 demonstrated efficacy on mCRC with microsatellite instability but remain ineffective alone in microsatellite stable tumour. 5-Fluorouracil and oxaliplatin were known to present immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate whether the addition of PD-L1 and CTLA-4 inhibition to oxaliplatin, fluorouracil and leucovorin (FOLFOX) increases treatment efficacy.MethodsThis phase II study (ClinicalTrials.gov NCT03202758) will assess the efficacy and safety of FOLFOX/D/T association in patients with mCRC (n=48). Good performance status patients (Eastern Cooperative Oncology Group <2) with untreated, RAS mutational status mCRC will be eligible. Prior adjuvant therapy is allowed provided recurrence is >6 months postcompletion. There is a safety lead in nine patients receiving FOLFOX/D/T. Assuming no safety concerns the study will go on to include 39 additional patients. Patients will receive folinic acid (400 mg/m²)/5-fluorouracil (400 mg/m² as bolus followed by 2400 mg/m2 as a 46-hour infusion)/oxaliplatin (85 mg/m2) every 14 days with D (750 mg) D1 every 14 days and T (75 mg) D1 every 28 days. After six cycles of FOLFOX only D/T will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is safety and efficacy according to progression-free survival (PFS); secondary endpoints include overall response rate and quality of life. Hypothesis is that a PFS of 50% at 6 months is insufficient and a PFS of 70.7% is expected (with α=10%, β=10%). Blood, plasma and tumour tissue will be collected and assessed for potential prognostic and predictive biomarkers.

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