scholarly journals Nintedanib plus docetaxel after progression on immune checkpoint inhibitor therapy: insights from VARGADO, a prospective study in patients with lung adenocarcinoma

2019 ◽  
Vol 15 (23) ◽  
pp. 2699-2706 ◽  
Author(s):  
Christian Grohé ◽  
Wolfgang Gleiber ◽  
Siegfried Haas ◽  
Christoph Losem ◽  
Harald Mueller-Huesmann ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Potential Clinical Benefit ◽  
Registration Number ◽  
Noninterventional Study ◽  
A Prospective Study

Aim: To assess outcomes in patients with advanced adenocarcinoma non-small-cell lung cancer who received nintedanib plus docetaxel after progression on prior chemotherapy followed by immune checkpoint inhibitor (ICI) therapy. Patients & methods: VARGADO is a prospective, noninterventional study. We describe initial data from a cohort of 22 patients who received nintedanib plus docetaxel after chemotherapy and ICI therapy. Results: Median progression-free survival with nintedanib plus docetaxel was 5.5 months (95% CI: 1.9–8.7 months). The objective response rate was 7/12 (58%) and the disease control rate was 10/12 (83%). Data for overall survival rate 12 months after the start of treatment (primary end point) are not yet mature and are not reported. Of 22 patients, 73% experienced drug-related adverse events; adverse events led to treatment discontinuation in 32% of patients. Conclusion: These data highlight the potential clinical benefit of nintedanib plus docetaxel in patients who failed prior ICI therapy.Trial registration number: NCT02392455

Effect of excess weight on immune-related adverse events from immune checkpoint inhibitor in lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21183-e21183
Author(s):  
Soravis Osataphan ◽  
Yu Jen Jan ◽  
Katherine A. Stafford ◽  
Prudence B. Lam
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
The United States ◽  
Normal Weight ◽  
Advanced Lung Cancer ◽  
Free Survival

e21183 Background: Immune checkpoint inhibitors (ICIs) are effective therapies for advanced lung cancer however they are also associated with immune-related adverse events (irAEs). Obesity has been shown to be correlated with both ICIs’ anti-tumor efficacy particularly in melanoma and non-small cell lung cancer (NSCLC). However, there have been conflicting reports between the relationship between BMI and the incidence of irAEs. Methods: We conducted a retrospective cohort study on the use of immune checkpoint inhibitor in advance lung cancer from Mount Auburn Hospital, a community-based teaching hospital in the United States, between 2016 to 2020. We studied the association between overweight (BMI of more than 25 kg/m2) versus normal weight patients (BMI 18.5 - 24.99 kg/m2) and incidence of irAEs or progression free survival. Results: A total of 51 patients with advanced lung cancer were treated with either Pembrolizumab, Nivolumab, Durvalumab or Atezolizumab. NSCLC accounted for 90.2% of the histological findings and adenocarcinoma represented 45.0% of the cohort. Among these patients 61.0% were classified as. There was a trend to increase in the incidence of irAEs in overweight compared to normal weight patients (48.3% vs. 25.0%, OR 1.91, 95% CI 0.56-6.99, p = 0.308). The most common irAEs in this cohort was thyroid dysfunction. The overweight group also had a higher baseline blood glucose level (120.5 ± 39.9 mg/dL vs. 92.9 ± 13.8 mg/dL, p < 0.01). However, no difference in progression free survival was found between the two groups (HR 1.19, 95%CI 0.58-2.42, p = 0.6). Conclusions: Although limited by sample size, here we reported a real-world experience where excessive weight may be an important predictor of irAEs development in patients with lung cancer.

Thyroid immune-related adverse events following immune checkpoint inhibitor treatment

2021 ◽  
Author(s):  
Christopher A Muir ◽  
Roderick J Clifton-Bligh ◽  
Georgina V Long ◽  
Richard A Scolyer ◽  
Serigne N Lo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Thyroid Dysfunction ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Overt Hypothyroidism ◽  
Female Sex ◽  
Younger Age

Abstract Background Thyroid dysfunction occurs commonly following immune checkpoint inhibition. The etiology of thyroid immune-related adverse events (irAEs) remains unclear and clinical presentation can be variable. This study sought to define thyroid irAEs following immune checkpoint inhibitor (ICI) treatment and describe their clinical and biochemical associations. Methods We performed a retrospective cohort study of thyroid dysfunction in patients with melanoma undergoing CTLA-4 and/or PD-1 based ICI treatment from Nov 1, 2009 to Dec 31, 2019. Thyroid function was measured at baseline and at regular intervals following the start of ICI-treatment. Clinical and biochemical features were evaluated for associations with ICI-associated thyroid irAEs. The prevalence of thyroid autoantibodies and the effect of thyroid irAEs on survival were analysed. Results A total of 1246 patients were included with a median follow-up of 11.3 months. 518 (42%) patients developed an ICI-associated thyroid irAE. Subclinical thyrotoxicosis (n=234) was the most common thyroid irAE, followed by overt thyrotoxicosis (n=154), subclinical hypothyroidism (n=61), and overt hypothyroidism (n=39). Onset of overt thyrotoxicosis occurred a median of 5 weeks (IQR 2-8) after receipt of first dose of ICI. Combination immunotherapy was strongly associated with development of overt thyrotoxicosis (OR 10.8, 95% CI 4.51-25.6 vs. CTLA-4 monotherapy; p&lt;0.001), as was female sex (OR 2.02, 95% CI 1.37-2.95; p&lt;0.001) and younger age (OR 0.83 per 10-years, 95% CI 0.72-0.95; p=0.007). By comparison, median onset of overt hypothyroidism was 14 weeks (IQR 8-25). The frequency of overt hypothyroidism did not differ between different ICI-types. The strongest associations for hypothyroidism were higher baseline TSH (OR 2.33 per mIU/L, 95% CI 1.61-3.33; p&lt;0.001) and female sex (OR 3.31, 95% CI 1.67-6.56; p=0.01). Overt thyrotoxicosis was associated with longer progression free survival (HR 0.68, 95% CI 0.49-0.94; p=0.02) and overall survival (HR 0.57, 95% CI 0.39-0.84; p=0.005). There was no association between hypothyroidism and cancer outcomes. Conclusions Thyroid irAEs are common and there are multiple distinct phenotypes. Different thyroid irAE subtypes have unique clinical and biochemical associations, suggesting potentially distinct etiologies for thyrotoxicosis and hypothyroidism arising in this context.

Association of immune-related adverse events with immune checkpoint inhibitor efficacy in pancancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14087-e14087 ◽  
Author(s):  
Qiyun Ou ◽  
Yunfang Yu ◽  
Haitao Zhong ◽  
Anlin Li ◽  
Yongjian Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Conventional Therapy ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Coefficient Of Determination

e14087 Background: Immune-related adverse events (irAEs) have been shown to be associated with the efficacy of immune checkpoint inhibitors in patients with advanced cancer, but the reported effect sizes have varied greatly in previous trials. We did a meta-analysis to assess immune checkpoint inhibitors efficacy and further explored the correlation of irAEs with efficacy in cancer. Methods: We systematically searched database inception to January, 2019 for randomized trials of immune checkpoint inhibitor in patients with advanced cancer that had available data for overall survival (OS) and progression-free survival (PFS), and irAEs. We calculated the pooled hazard ratios (HRs) and 95% confidence intervals [CIs] using a random-effects model, and assessed the association between the irAEs and PFS or OS using coefficient of determination ( R²). The PROSPERO registry number is CRD42017075610. Results: Thirty eight trials with 19,521 patients were included. Compared with conventional therapy, anti-PD-1 or PD-L1 combined with conventional therapy significantly enhanced survival (HR = 0.62, 95% CI 0.53 to 0.72 for PFS; HR = 0.71, 95% CI 0.58 to 0.87 for OS), and anti-PD1 or PD-L1 combined with anti-CTLA4 (HR = 0.75, 95% CI 0.63 to 0.90 for PFS). Anti-CTLA4 plus conventional therapy prolonged PFS (HR = 0.80, 95% CI 0.72 to 0.89) and OS (HR = 0.80, 95% CI 0.66 to 0.96) than conventional therapy alone. Anti-PD1 or PD-L1 outperformed anti-CTLA4 on OS (HR = 0.68, 95% CI 0.57 to 0.81). Significant correlation between treatment efficacy and irAEs was only identified in pneumonitis ( R2 0.59, P = 0.026 for PFS) and diarrhea ( R2 0.22, P = 0.006 for OS). Conclusions: We recommended the concurrent use of immune checkpoint inhibitor and conventional therapy or dual immunotherapy as the most appropriate regimens for advanced cancer. Furthermore, development of pneumonitis and diarrhea were associated with survival outcome of immune checkpoint inhibitors in patients with advanced cancer.

scholarly journals Immune‐Related Hematologic Adverse Events in the Context of Immune Checkpoint Inhibitor Therapy

2021 ◽  
Author(s):  
Antoine N. Saliba ◽  
Zhuoer Xie ◽  
Alexandra S. Higgins ◽  
Xavier A. Andrade‐Gonzalez ◽  
Harry E. Fuentes‐Bayne ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

scholarly journals Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1151
Author(s):  
Shinsuke Suzuki ◽  
Satoshi Toyoma ◽  
Yohei Kawasaki ◽  
Koh Koizumi ◽  
Nobuko Iikawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Grade 3

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

Systemic Treatment of Cutaneous Adverse Events After Immune Checkpoint Inhibitor Therapy

Dermatitis ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Alexandria M. Brown ◽  
Wylie Masterson ◽  
Jonathan Lo ◽  
Anisha B. Patel
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Systemic Treatment ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy
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