scholarly journals Association of Systemic Steroid Treatment and Outcome in Patients Treated with Immune Checkpoint Inhibitors: A Real-World Analysis

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5789
Author(s):  
Agnese Paderi ◽  
Elisabetta Gambale ◽  
Cristina Botteri ◽  
Roberta Giorgione ◽  
Daniele Lavacchi ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Detrimental Effect ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Steroid Treatment ◽  
Systemic Steroid ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival

Background: Immune-related adverse events (irAEs) are inflammatory side effects, which can occur during immune-checkpoint(s) inhibitors (ICIs) therapy. Steroids are the first-line agents to manage irAEs because of their immunosuppressive properties. However, it is still debated whether or when steroids can be administered without abrogating the therapeutic efforts of immunotherapy. Methods: We retrospectively evaluated 146 patients with metastatic non-small cell lung cancer (NSCLC), melanoma and renal cell carcinoma (RCC) treated with ICIs. We assessed the progression-free survival (PFS) of patients treated with steroids due to an irAE compared to a no-steroid group. Results: The early treatment with steroid (within the first 30 days from the beginning of immunotherapy) was not related to a shorter PFS (p = 0.077). Interestingly, patients who were treated with steroids after 30 days from the start of immunotherapy had significantly longer PFS (p = 0.017). In a multivariate analysis, treatment with steroids after 30 days was an independent prognostic factor for PFS (HR: 0.59 [95% CI 0.36–0.97], p = 0.037). Conclusions: This retrospective study points out that early systemic steroids administration to manage irAEs might not have a detrimental effect on patient clinical outcome in NSCLC, melanoma and RCC patients.

scholarly journals Efficacy of immune checkpoint inhibitor therapy in patients with RET fusion-positive non-small-cell lung cancer

Immunotherapy ◽  
2021 ◽  
Author(s):  
Naleen Raj Bhandari ◽  
Lisa M Hess ◽  
Yimei Han ◽  
Yajun E Zhu ◽  
Anthony N Sireci
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival

Aim: To describe outcomes of patients with RET fusion-positive non-small-cell lung cancer (NSCLC) who received immune checkpoint inhibitor (ICI)-based treatments in the US. Patients & methods: Using de-identified Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic and Guardant Health databases, treatment patterns and outcomes of 69 patients with advanced/metastatic RET fusion-positive NSCLC who received ICI-based treatment were described. Results: Median real-world progression-free survival and overall survival months were 4.2 (95% CI: 1.4–8.4) and 19.1 (6.9–not reached), respectively, among patients in Clinico-Genomic database (n = 17) receiving first-line ICI-based therapy. In the Guardant Health database, progression-free survival was unavailable, and the median overall survival was not reached (n = 29). Conclusion: Outcomes associated with ICI-based treatments in the first-line setting among patients with RET fusion-positive NSCLC are consistent with unselected populations reported in literature.

scholarly journals The efficacy and safety of immune checkpoints inhibitors plus radiotherapy as a combination therapy for advanced non-small cell lung carcinoma: a meta-analysis

2020 ◽  
Author(s):  
Dan Yang ◽  
DaiRong Li ◽  
LuLu Wang ◽  
LuMi Huang ◽  
JianLin Long ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Radiotherapy Group

Abstract BackgroundImmune checkpoint inhibitors have showed good efficacy in advanced non-small-cell lung cancer(NSCLC). This meta-analysis was conducted to explore the therapeutic efficacy and safety of immune checkpoint inhibitors combined with radiotherapy for patients with advanced NSCLC.MethodsWe used many proper keywords to perform a systematic search in databases and performed a meta-analysis of trials that conducted immune checkpoint inhibitors plus radiotherapy as a treatment for advanced non-small-cell lung cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.ResultsTen trials were finally included in this meta-analysis. The combined ORR and DCR was 34% (19%-49%) and 72% (65%-79%). The combined six-month progression-free survival rates (PFSR6m) and one-year overall survival rate(OSR1y) were 50.0% (29.4%-72.8%) and 59.0% (48%-69%). Immune checkpoint inhibitors plus radiotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.64; 95% CI 0.46–0.90; P = 0.01), OS (HR, 0.62; 95% CI 0.46–0.85; P = 0.003). In subgroup analyses, the combined ORR was 31.5% (16.4%-46.6%), combined DCR was 72.1% (63.3%-80.9%), combined PFS6m was 50.0% (20.6%-79.5%) and combined OSR1y was 59.7% (48.1%-71.2%) for anti-PD-1/PD-L1 antibody plus radiotherapy. The combined ORR was 19.5% (9.1%-29.8%) for anti-CTLA4 antibody plus radiotherapy. The combined PFS6m and OSR1y were 58.9% (26.2%-91.7%) and 59.7% (29.7%-89.8%) respectively for the concurrent therapy group. And the combined PFS6m and OS1y were 55.2% (41.6%-68.8%) and 55.7% (42.1%-69.3%) for sequential therapy. For the low-dose radiotherapy group. The combined PFS6m and OS1y were 45.9% (27.0%-64.8%) and 51.6% (37.5%-65.6%). The combined PFS6m and OS1y were 71.1% (37.9%-104.4%) and 67.4% (29.2%-105.6%) separately for high-dose radiotherapy group. When using as first-line therapy. The combined ORR was 53.8% (23.6%-84.1%) and combined ORR was 76.5% (65.0%-88.1%). While as subsequent therapy, the combined ORR and DCR were 25.9% (14.7%-37.2%) and 69.9% (60.9%-78.9%). The combined PFS6m and OS1y were 51.1% (40.3%-61.9%) and 51.8% (40.9%-62.7%).ConclusionsImmune checkpoint inhibitors plus radiotherapy might be an effective and tolerable option as a treatment for advanced NSCLC.

scholarly journals Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2352
Author(s):  
Francesco Fiorica ◽  
Umberto Tebano ◽  
Milena Gabbani ◽  
Mariasole Perrone ◽  
Sonia Missiroli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Metastatic Nsclc ◽  
Nsclc Patients

Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this combination on the increase in overall and progression-free survival. Data sources: The MEDLINE and CANCERLIT (1970–2020) electronic databases were searched, and the reference lists of included studies were manually searched. Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy. Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method. Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64–0.88; p = 0.0003) and 0.85 (95% CI 0.78–0.93; p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61–0.87; p = 0.0005) and RR 0.82 (95% CI 0.67–0.99; p = 0.04), respectively). Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone.

scholarly journals The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangyun Liu ◽  
Yixuan Zhang ◽  
Miaowen Liu ◽  
Ruoxin Xu ◽  
Fengming Yi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients. Methods We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS). Results We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia. Conclusions The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.

scholarly journals Treatments of Advanced Non‑Small Cell Lung Cancer (NSCLC) in an Italian Center: Drug Utilization and the Treatment Costs of Innovative Drugs

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Francovito Piantedosi ◽  
Raffaela Cerisoli ◽  
Ciro Battiloro ◽  
Francesca Andreozzi ◽  
Fabiana Vitiello ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Small Cell ◽  
Line Treatment ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line

AIM: To provide an updated picture of the therapies most commonly used in the advanced Non-Small Cell Lung Cancer (NSCLC) setting, together with the relevant costs.METHODS: This study considered the clinical records of patients affected by stage IIIb and IV NSCLC treated in the AORN dei Colli - Plesso Monaldi in Naples during the period January 2016-July 2017 and diagnosed since 2014, as well as the pathology lab database. Multivariate analyses were performed in order to identify the main predictors of time to next treatment and the main cost drivers.RESULTS: Data were collected on 575 patients, who were mainly affected by adenocarcinoma (62%) and squamous cell carcinoma (34%). 64% of patients were reported having been tested for molecular biomarkers (among the patients tested, 13% were EGFR+, 4% Alk t, and 1% ROS1 t). In accordance with the international guidelines, chemotherapy – as single agent or platinum-based doublets – was the prevalent first-line treatment, except among EGFR+ and ROS1 t patients, for whom the target therapy was authorized as first-line therapy. As second-line treatment, the target therapy and immune checkpoint inhibitors (nivolumab) were the most commonly used treatments. Drug expenditure per patient was remarkably higher in mutated patients (€ 29,053) versus wild-type patients, or patients with unknown mutational status (€ 11,854), who received just chemotherapy. The costs sustained in 2017 are proportionally higher than those sustained in 2016, mainlydue to the increasing eligibility to target therapy and immune checkpoint inhibitors and the wider biomarker analysis performed. From multivariate analyses, among the predictors of a longer time to next treatment (TTNT) were a better performance status and target therapy both in first and second line. The therapy for squamous cell carcinoma and other nonadeno histotypes turned out to be less expensive in patients treated just in the first line than that for adenocarcinoma and adenosquamous carcinoma. The use of immune checkpoint inhibitors in the second line results in increased costs compared to the use of chemotherapy. Also the target therapy in the first line results in an increase in the total costs with respect to chemotherapy in patients who received just a first-line therapy.CONCLUSIONS: Generally, in this study population, the treatments administered are in accordance with the international guidelines. The costs borne by the Health Systems are higher for the target therapy and the immune checkpoint inhibitors.

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