scholarly journals 25 Potential role of serum proteome in predicting immune-related adverse events from immunotherapy in non-small cell lung cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A29-A29
Author(s):  
Leeseul Kim ◽  
Young Kwang Chae ◽  
Dong-Uk Lee
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Primary Immune Response ◽  
Small Cell Lung ◽  
Serum Proteome ◽  
Proteome Level ◽  
Nsclc Patients

BackgroundPredicting immune-related adverse events (irAEs) in early stage is being emphasized even more. Host response to disease is reflected in serum proteome level and that allows serum proteome level as a new marker to explore response to immunotherapy. With the help of a serum-based proteomics test, Primary Immune Response (PIR), we are accessing the correlations between developing irAEs and immunotherapy in non-small cell lung cancer (NSCLC) patients.MethodsData of 48 consented NSCLC patients with baseline PIR test done within one week prior to the start of immunotherapy were collected. Samples were grouped into either sensitive or intermediate/resistant (not sensitive) by PIR classification. We analyzed the durations from the immunotherapy initiation to the first episode of irAE. IrAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsAmong the 48 NSCLC patients, 19 patients (39%) experienced one or more irAEs with the majority classified as either grade 1 (n=7, 36%) or grade 2 (n=10, 52%). PIR-sensitive group showed no difference in irAE free period compared to PIR-not sensitive (p=0.92, HR=0.95, 95% CI=00.3212 to 2.834). The median ‘Time to first irAE’ were undefined and 24 in PIR-sensitive and PIR-not sensitive, respectively.ConclusionsOur results demonstrated PIR-sensitive patients are not likely to tolerate immunotherapy longer without developing irAEs.

scholarly journals Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lea Daniello ◽  
Mariam Elshiaty ◽  
Farastuk Bozorgmehr ◽  
Jonas Kuon ◽  
Daniel Kazdal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Palliative Radiotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Treatment Type ◽  
Nsclc Patients

IntroductionPD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.MethodsWe analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.ResultsIrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001).ConclusionsApproximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.

802 Ramucirumab plus atezolizumab in patients with stage IV non-small cell lung cancer previously treated with immune checkpoint blockade

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A851-A851
Author(s):  
Brett Herzog ◽  
Saiama Waqar ◽  
Siddhartha Devarakonda ◽  
Jeffrey Ward ◽  
Ramaswamy Govindan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Small Cell ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundT-cell trafficking to the tumor is inhibited via vascular endothelial growth factor (VEGF)-mediated down-regulation of important adhesion molecules on tumor-associated blood vessels and progression of disease on immune checkpoint blockers (ICBs) has been associated with decreased tumor-infiltrating immune cells.1 2 We hypothesized that inhibiting VEGF signaling through its receptor, VEGFR2, would increase intratumoral T cells. Therefore we sought to evaluate the combination of ramucirumab, an anti-VEGF receptor 2 monoclonal antibody, and atezolizumab in patients with advanced-stage, non-small cell lung cancer (NSCLC) patients who have previously progressed on at least one line of ICB. Here, we report on the first twelve patients enrolled on trial.MethodsAdvanced stage NSCLC patients with an ECOG performance status of ≤1 who had previously been treated with ICBs were eligible with no limitation on prior lines of ICB therapy. Patients with untreated brain metastasis, recent hemoptysis, gastrointestinal bleeding or perforation or fistula were excluded. The study was conducted with a two-stage MiniMax design. Peripheral blood and repeated biopsy, when feasible, were collected for correlative analysis.ResultsTwelve patients were enrolled in the first stage of the trial. The median age was 68 (range 47-78), 10 of the patients are female, and 10 had non-squamous histology. Patients had an average of 3.5 prior lines of therapy and 1.6 lines of prior immunotherapy. Overall, treatment was well-tolerated with no grade 3 or 4 adverse events. The most common adverse events were grade 1 or 2 hypertension (35%), nausea (25%) and vomiting (25%). There were no objective responses and 11 patients (91%) achieved stable disease. The median progression-free survival is 3 months with 3 patients (25%) on trial for more than 12 months. The median overall survival (OS) at the time of the latest data cutoff on 9/15/20 is 11.5 months.ConclusionsThe preliminary data from our study showed that combination of ramucirumab and atezolizumab is well-tolerated and associated with prolonged overall survival in a subset of heavily pretreated patients who progressed on prior ICB. The trial is still accruing patients and exploratory analyses are planned.Ethics ApprovalThe study was approved by the Washington University Institutional Review Board.ReferencesDirkx AE, oude Egbrink MG, Castermans K, et al. Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. FASEB J 2006;20(6):621-630.Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014;515(7528):563-567.

A phase II study of vorolanib in combination with toripalimab in patients with non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21053-e21053
Author(s):  
Jun Zhao ◽  
Jianjie Li ◽  
Hanxiao Chen ◽  
Xue Yang ◽  
Jia Zhong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e21053 Background: VEGF promotes an immunosuppressive microenvironment and contributes to resistance of immune checkpoint inhibitors in cancer treatment. VEGF inhibitors have been shown to enhance efficacy of checkpoint inhibitors in clinical studies. Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1). This phase II study aims to evaluate efficacy and safety of the combination of vorolanib and JS001 in non-small cell lung cancer (NSCLC) patients who progressed with prior first-line standard therapy. Methods: This single-arm, single-center, phase II study (NCT03848611) enrolls NSCLC patients with measurable disease (RECIST 1.1) and Eastern Cooperative Oncology Group performance status ≤ 1, regardless of PD-L1 status. 15 patients received 150 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks while 3 patients received 100 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). Results: Between April 2019 and July 2020, 18 patients were enrolled. Median age was 64 years. 9 of 18 patients (50%) were adenocarcinoma and 9 of 18 patients (50%) were squamous. Males account for 83% (15/18) with 4 non-smokers among the male patients. At the data cutoff (January 11, 2021), we observed 2 (11%) confirmed and 1 (6%) unconfirmed partial response (PR), 6 (33%) stable disease (SD) and 9 (50%, including 2 PR of the target lesions) progression disease (PD). Tumor shrinkage was seen in 6 (33%) of the 18 patients. Two (11%) patients were still on the study drugs. Interestingly, all the patients with confirmed PR or PR of the target lesions were squamous histology. The most common treatment-related adverse events were proteinuria (67%), elevated ALT (60%), elevated AST (53%), hypertension (40%), and increased bilirubin (40%). Grade 3 adverse events include elevated ALT (20%), elevated AST (20%), liver function damage (13%), elevated GGT (7%), fatigue (7%), bellyache (7%), ruptured and infected tumor (7%), and dysphagia (7%). One Grade 4 adverse event was pulmonary embolism. Conclusions: Vorolanib with toripalimab showed a promising antitumor activity with acceptable safety profiles for patients with NSCLC. We hypothesized that the potential benefits of combination therapy for patients with squamous cell carcinoma may be better than those for patients with adenocarcinoma, and the study is ongoing. Clinical trial information: NCT03848611.

Analysis of immune-mediated reactions in patients with non-small cell lung cancer treated with nivolumab and its association with effectiveness

2021 ◽  
pp. 107815522110674
Author(s):  
Susana Cortijo-Cascajares ◽  
Ana Cristina Cercós-Lletí ◽  
Sara Ortiz-Pérez ◽  
José Manuel Caro-Teller ◽  
José Miguel Ferrari-Piquero
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Strong Predictor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Number Of Patients ◽  
Nsclc Patients

Objective To study immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab, as well as to assess whether these reactions could be predictors of further effectiveness of therapy. Methods Retrospective, observational and longitudinal study. All NSCLC patients who received nivolumab between February 2015-May 2020 were included. In terms of safety, irAEs and their severity were registered and to evaluate the effectiveness, overall survival (OS) and progression free survival (PFS) were calculated. Results 75 patients were included. 32 patients (43%) were reported irAES. Mainly the irAEs affected the skin (36%). Followed by pneumonitis (20%), gastrointestinal reactions (12%), endocrine (12%) and hepatitis (12%). Regarding severity, 92% were moderate. The median PFS was 9.49 months on the group with irAEs versus 1.99 months on the group without irAEs group (p < 0.0001). The median OS was 17.44 months versus 7.67 months respectively (p = 0.0001). According to the incidence of irAEs developed ( = > 2 vs. 1 vs. 0), the median PFS was 20.53 versus 5.35 versus 1.99 months respectively (p < 0.0001). The median OS was 23.41 versus 15.80 versus 7.67 months, respectively (p = 0.0002) Conclusion In a significant number of patients irAEs occur, generally of grade 1–2 severity, affecting mainly the skin, lungs and gastrointestinal system. We confirm that the development of irAEs in patients with NSCLC treated with nivolumab is a strong predictor of treatment effectiveness in both PFS and OS, with statistically significant results. On those patients who experience two or more immunorelated adverse events the greatest benefit has been observed.

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