Concurrence of nivolumab-induced interstitial lung disease and cancer invasion.
Ontology highlight
ABSTRACT:
SUBMITTER: Kanai O
PROVIDER: S-EPMC5553297 | biostudies-other | 2017 Nov
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. Following nivolumab as a sixth-line treatment, an EGFR-T790M-encoding mutation in EGFR exon 20 was identified by re-biopsy. Osimertinib was therefore initiated as a seventh-line treatment. A partial response was subsequently noted; however, 63 days after initiation of the treatment the patient presented with dyspnea with decreased oxygenation in the absence of fever and sputum. A computed tomography scan revealed the emergence of ground-glass opacities with bronchiectasis in both lungs, and a diagnosis of ILD due to osimertinib was made. Following steroid pulse therapy with discontinuation of osimertinib, the patient's chest findings and respiratory condition improved. Therefore, it is considered that anti-PD-1 therapies may be associated with a risk of ILD during subsequent osimertinib treatment.
| S-EPMC5543261 | biostudies-other
Project description:Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground-glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, three had peritumoral-GGO, and five had a change in radiographic pattern from non-DAD at the onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.
| S-EPMC8019215 | biostudies-literature
Project description:BackgroundNivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, has shown survival benefit in clinical trials of various malignant tumors. Nivolumab-induced pneumonitis is major immune-related adverse event (irAE) that is occasionally serious and life-threatening. The aim of this study was to examine the association between pre-existing interstitial lung disease (ILD) on chest computed tomography (CT) and nivolumab-induced pneumonitis among different types of solid tumors.MethodsWe retrospectively collected the clinical data of 311 patients who were diagnosed with non-small cell lung cancer (NSCLC), head and neck cancer (HNC), or gastric cancer (GC), and treated with nivolumab monotherapy. Patients who underwent chest CT immediately before starting nivolumab without previous thoracic radiotherapy or other immune checkpoint inhibitors were eligible. We collected baseline patient characteristics and assessed pre-existing ILD on baseline chest CT.ResultsFinally, 188 patients were included in the analysis: 96 patients with NSCLC, 43 patients with HNC, and 49 patients with GC. NSCLC patients had a significantly higher rate of pre-existing ILD compared with HNC/GC patients (P = 0.047). Nivolumab-induced pneumonitis occurred in 11.7% (22 of 188), including 14.6% (14 of 96) of NSCLC, and 8.7% (8 of 92) of HNC/GC. Univariate and multivariate logistic regression analyses revealed that pre-existing ILD (odds ratio, 5.92; 95% confidence interval (CI), 2.07-18.54, P = 0.0008) and male sex (odds ratio, 5.58; 95% CI, 1.01-104.40, P = 0.049) significantly increased the risk of nivolumab-induced pneumonitis.ConclusionOur results indicated that pre-existing ILD and male sex are risk factors for nivolumab-induced pneumonitis in solid tumors.
| S-EPMC8369733 | biostudies-literature
Project description:BackgroundUp to 10% of patients with advanced non-small cell lung cancer (aNSCLC) have pre-existing interstitial lung disease (ILD). These patients are usually excluded from immunotherapy clinical trials. Consequently, knowledge on outcomes following nivolumab treatment in these patients remains limited. The primary objective of this study was to evaluate survival outcome following nivolumab treatment in ILD patients with pre-treated aNSCLC in the real-world setting.Patients and methodsThe study included all patients with aNSCLC recorded in the French hospital database, starting nivolumab in 2015-2016. Patients were stratified by pre-existing ILD and three subgroups were studied [auto-immune or granulomatous (AI/G) ILD, other known causes ILD and idiopathic ILD]. Time to discontinuation of nivolumab treatment [time to treatment duration (TTD)] and overall survival (OS) were estimated using Kaplan-Meier survival analysis.ResultsOf 10,452 aNSCLC patients initiating nivolumab, 148 (1.4%) had pre-existing ILD. Mean age at nivolumab initiation was 64.6 ± 9.4 years in ILD and 63.8 ± 9.6 years in non-ILD. Compared to non-ILD, patients in the ILD group were more frequently men (p < 0.05) and had more comorbidities (p < 0.001). There was no significant difference between ILD and non-ILD groups for median TTD (2.5 versus 2.8 months; p = 0.6) or median OS (9.6 versus 11.9 months; p = 0.1). Median OS in AI/G ILD (n = 14), other known causes ILD (n = 75), and idiopathic ILD (n = 59) were 8.6, 10.7, and 9.6 months, respectively.ConclusionIn this large cohort of aNSCLC patients with ILD, outcomes are similar to those obtained in the non-ILD population. Immunotherapy could be beneficial for these patients.
| S-EPMC9893351 | biostudies-literature
Project description:Importance:Nivolumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non-small cell lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined safety profiles, our experience with immune checkpoint inhibitors is still growing, particularly regarding the use of combinations of different classes of antitumor agents, including both the concomitant and sequential use of such agents. Objective:To determine whether nivolumab increases EGFR-TKI-associated interstitial pneumonitis (IP). Design, Setting, and Participants:A database study of 20 516 participants with NSCLC in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, performed between April 2015 and March 2017. Main Outcomes and Measures:We compared the incidence of EGFR-TKI-associated IP in patients receiving and not receiving nivolumab treatment. Results:The mean (SD) age of participants treated with EGFR-TKI, with and without nivolumab, was 64.4 (15.5) and 68.9 (11.8) years, respectively, and the proportion of men was 40.0% and 53.8%, respectively. Of the 20 516 participants with NSCLC, 985 cases (4.80%; 95% CI, 4.51-5.10) developed IP. Of 5777 patients treated with EGFR-TKI, 265 developed IP (4.59%; 95% CI, 4.06-5.16). Of 70 patients treated with both EGFR-TKI and nivolumab, 18 developed IP (25.7%; 95% CI, 16.0-37.6). The adjusted odds ratio for an interaction between EGFR-TKI and nivolumab was 4.31 (95% CI, 2.37-7.86; P < .001), suggesting the existence of an interaction. When we further stratified the patients by treatment with and without nivolumab, the odds ratio of EGFR-TKI-associated IP in cases with and without nivolumab treatment was 5.09 (95% CI, 2.87-9.03) and 1.22 (95% CI, 1.00-1.47), respectively. Conclusions and Relevance:We found a higher proportion of reports of IP for nivolumab in combination with EGFR-TKI vs treatment with either drug alone. Owing to the limitations of this study, the results warrant further confirmation. However, careful consideration should be given to the possibility of an increased risk of IP when EGFR-TKI is administered in combination with nivolumab, including concomitant and sequential use, and careful monitoring for IP is recommended.
| S-EPMC5885195 | biostudies-literature
Project description:BackgroundDrug-induced interstitial lung disease (DIILD) is a form of interstitial lung disease resulting from exposure to drugs causing inflammation and possibly interstitial fibrosis. Antineoplastic drugs are the primary cause of DIILD, accounting for 23%-51% of cases, with bleomycin, everolimus, erlotinib, trastuzumab-deruxtecan and immune checkpoint inhibitors being the most common causative agents. DIILD can be difficult to identify and manage, and there are currently no specific guidelines on the diagnosis and treatment of DIILD caused by anticancer drugs.ObjectiveTo develop recommendations for the diagnosis and management of DIILD in cancer patients.MethodsBased on the published literature and their clinical expertise, a multidisciplinary group of experts in Italy developed recommendations stratified by DIILD severity, based on the Common Terminology Criteria for Adverse Events.ResultsThe recommendations highlight the importance of multidisciplinary interaction in the diagnosis and management of DIILD. Important components of the diagnostic process are physical examination and careful patient history-taking, measurement of vital signs (particularly respiratory rate and arterial oxygen saturation), relevant laboratory tests, respiratory function testing with spirometry and diffusing capacity of the lung for carbon monoxide and computed tomography/imaging. Because the clinical and radiological signs of DIILD are often similar to those of pneumonias or interstitial lung diseases, differential diagnosis is important, including microbial and serological testing to exclude or confirm infectious causes. In most cases, management of DIILD requires the discontinuation of the antineoplastic agent and the administration of short-term steroids. Steroid tapering must be undertaken slowly to prevent reactivation of DIILD. Patients with severe and very severe (grade 3 and 4) DIILD will require hospitalisation and often need oxygen and non-invasive ventilation. Decisions about invasive ventilation should take into account the patient's cancer prognosis.ConclusionsThese recommendations provide a structured step-by-step diagnostic and therapeutic approach for each grade of suspected cancer-related DIILD.
| S-EPMC8881716 | biostudies-literature
Project description:BACKGROUND:Interstitial lung disease (ILD) is a group of diffuse lung diseases that mainly involve the interstitial and alveolar cavities and result in loss of alveolar-capillary functional units, leading to restrictive ventilatory dysfunction and diffusion impairment. There was an increased incidence of lung cancer on the basis of ILD, and perioperative risk of patients with lung cancer combined with ILD (LC-ILD) was significantly increased. The aim of this study is to summarize the safety and experience of surgical treatment of LC-ILD. METHODS:A retrospective analysis was performed on 23 patients with LC-ILD who underwent pneumonectomy in Beijing Hospital from January 2012 to December 2019, and their clinical manifestations, image feature, pathology, surgical safety, perioperative complications and treatment experience were summarized. RESULTS:A total of 23 patients were included in this study, including 20 males (87.0%) with an average age of (69.1±7.8) years, and 19 cases (82.6%) were smokers. Of the ILD types, 14 cases (60.9%) were idiopathic pulmonary fibrosis, 7 cases (30.4%) were idiopathic nonspecific interstitial pneumonia, and 2 (8.7%) were interstitial lung disease associated with connective tissue diseases. The pathology of lung cancer included adenocarcinoma (30.4%, 7/23), small cell carcinoma (30.4%, 7/23), squamous cell carcinoma (26.1%, 6/23), small cell carcinoma mixed with squamous cell carcinoma (4.3%, 1/23) and large cell neuroendocrine carcinoma (8.7%, 2/23). Surgical approaches included video assisted thoracoscopy (69.6%, 16/23) and anterolateral thoracotomy (30.4%, 7/23), with lobectomy (52.2%, 12/23), double lobectomy (4.3%, 1/23), and sublobectomy (39.1%, 9/23). There were 11 cases (47.8%) of postoperative complications, including 8 cases (34.8%) of pulmonary complications, 4 cases (17.4%) of acute exacerbation of ILD (AE-ILD), 6 cases (26.1%) of atrial fibrillation, and 1 case (4.3%) of acute left ventricular dysfunction. The 90-day mortality is 8.7% (2/23) and the cause of death was acute exacerbation of ILD. CONCLUSIONS:Most of LC-ILD were elderly patients with multiple comorbidities and decreased pulmonary function, leading to significantly increased surgical risk. The ILD should be fully evaluated and controlled before surgery, intraoperative trauma should be minimized, and special attention should be paid to pulmonary complications and AE-ILD after surgery. Postoperative AE-ILD has a poor prognosis and glucocorticoids may be effective. Early diagnosis and treatment is the key to treatment of AE-ILD.
| S-EPMC7260382 | biostudies-literature
Project description:ObjectiveLung cancer patients with interstitial lung disease (ILD) are prone for higher morbidity and mortality and their treatment is challenging. The purpose of this study is to investigate whether the survival of lung cancer patients is affected by the presence of ILD documented on CT.Materials and methods146 patients with ILD at initial chest CT were retrospectively included in the study. 146 lung cancer controls without ILD were selected. Chest CTs were evaluated for the presence of pulmonary fibrosis which was classified in 4 categories. Presence and type of emphysema, extent of ILD and emphysema, location and histologic type of cancer, clinical staging and treatment were evaluated. Kaplan-Meier estimates and Cox regression models were used to assess survival probability and hazard of death of different groups. P value < 0.05 was considered significant.Results5-year survival for the study group was 41% versus 48% for the control group (log-rank test p = 0.0092). No significant difference in survival rate was found between the four different categories of ILD (log-rank test, p = 0.195) and the different histologic types (log-rank test, p = 0.4005). A cox proportional hazard model was used including presence of ILD, clinical stage and age. The hazard of death among patients with ILD was 1.522 times that among patients without ILD (95%CI, p = 0.029).ConclusionPatients with lung cancer and CT evidence of ILD have a significantly shorter survival compared to patients with lung cancer only. Documenting the type and grading the severity of ILD in lung cancer patients will significantly contribute to their challenging management.
| S-EPMC8423282 | biostudies-literature
Project description:IntroductionInterstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear.MethodsRetrospective study of 913 patients who received osimertinib treatment for EGFR mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge.ResultsOf 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7-12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6-15.0).ConclusionsThe risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.
| S-EPMC10999481 | biostudies-literature
Project description:This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual European Respiratory Society Congress in Vienna, Austria. Since the recent international guidelines for the management of idiopathic pulmonary fibrosis (IPF), important new evidence is available. The anti-fibrotic drug pirfenidone has been recently approved in Europe. Other pharmacological agents, especially nintedanib, are still being tested. The so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended as treatment. Although the clinical course of IPF is highly variable, novel tools have been developed for individual prediction of prognosis. Acute exacerbations of IPF are associated with increased mortality and may occur with higher frequency in IPF patients with associated pulmonary hypertension. Interstitial lung disease associated with connective tissue disease has been definitely established to have a better long-term survival than IPF. A subset of patients present with symptoms and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given autoimmune disease; this condition is associated with a higher prevalence of nonspecific interstitial pneumonia pattern, female sex and younger age, although survival relevance is unclear.
| S-EPMC9487426 | biostudies-literature