scholarly journals Effect of Systemic Steroid Use for Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Receiving PD-1 Blockade Drugs

2021 ◽  
Vol 10 (16) ◽  
pp. 3744
Author(s):  
Atsuto Mouri ◽  
Kyoichi Kaira ◽  
Ou Yamaguchi ◽  
Kousuke Hashimoto ◽  
Yu Miura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Adrenal Insufficiency ◽  
Small Cell ◽  
Systemic Steroid ◽  
Small Cell Lung ◽  
Steroid Use ◽  
Systemic Steroids ◽  
Programmed Death

Objectives: Programmed death-1(PD-1)/programmed death ligand-1 (PD-L1) antibodies have clinical benefits for cancer patients facing immune-related adverse events (irAEs). However, the effect of steroid use on the prognosis of patients with non-small cell lung cancer (NSCLC) receiving PD-1 blockade remains unclear. Methods: NSCLC patients with complete response (CR)/partial response (PR) or stable disease (SD)/not evaluable (NE) status plus progression-free survival (PFS) of 180 days after PD-1 blockade from December 2015 to December 2018 were retrospectively registered in our study and were divided into two groups: those with and without systemic steroid use for irAEs. Results: In total, 126 patients who had benefitted from PD-1 blockade were enrolled in our study; among them, 44 received systemic steroids for irAEs, and 82 had no adverse events or, if they did, did not receive systemic steroids. Among the 44 patients requiring steroids, interstitial lung disease (ILD), adrenal insufficiency, diarrhea, and liver dysfunction were observed in 19, 9, 4, and 4 patients, respectively. More side effects were observed in the group treated by steroids. The median PFS and overall survival (OS) in patients with and without systemic steroid use were 11.7 and 16.0 months (p < 0.037) and 35.0 and 41.0 months (p < 0.28), respectively. In univariate and multivariate analyses of survival, systemic steroid treatment for irAEs was significantly associated with PFS. The occurrence of ILD, adrenal insufficiency, and fever was significant in patients who used systemic steroids for irAEs. Conclusions: Patients administered systemic steroids for irAEs due to PD-1 blockade treatment exhibited shorter PFS than those who were not. Systemic steroids might affect survival after PD-1 blockade even for patients who once acquired its clinical benefit.

scholarly journals Efficacy and Feasibility of Programmed Death-1/Programmed Death Ligand-1 Blockade Therapy in Non-Small Cell Lung Cancer Patients With High Antinuclear Antibody Titers

2021 ◽  
Vol 11 ◽  
Author(s):  
Atsuto Mouri ◽  
Kyoichi Kaira ◽  
Ou Yamaguchi ◽  
Kosuke Hashimoto ◽  
Yu Miura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Antinuclear Antibody ◽  
Small Cell ◽  
Negative Group ◽  
Small Cell Lung ◽  
Positive Group ◽  
Programmed Death

BackgroundImmune checkpoint inhibitor (ICI) therapy has been described to markedly improve patient survival. However, reports describing the antitumor therapeutic efficacy and safety of ICIs in patients with autoantibodies are scarce.MethodsThis study examined the efficacy and feasibility of ICIs in antinuclear antibody (ANA)-positive patients with non-small cell lung cancer (NSCLC). An ANA titer greater than 1:40 and 1:80 was defined as positive and high, respectively. Patients who were treated with ICIs at Saitama Medical University, International Medical Center between January 2016 and December 2018 were retrospectively reviewed.ResultsOne hundred and nineteen of the 266 patients (44.7%) who received nivolumab, pembrolizumab, and atezolizumab had positive ANA titers. Their median age was 69 (range, 39–84) years. The overall response rate of the ANA-positive patients was 35.9% (37/103), which was not less than that of the ANA-negative group. The median progression-free survival in the ANA-positive group was 6.3 months versus 4.3 months in the ANA-negative group (p = 0.08). Twenty-seven ANA-positive patients (10.2%) had high ANA titers. However, ICI efficacy was not decreased in these patients. Regardless of the cutoff of ANA titers (1:40 or 1:80), the rate of patients who experienced adverse events were not significantly different between the two groups.ConclusionThe administration of ICIs to ANA-positive patients has clinical benefits. The prevalence of adverse events in the ANA-positive group was not higher than that in the ANA-negative group.

scholarly journals Safety of Programmed Death–1 Pathway Inhibitors Among Patients With Non–Small-Cell Lung Cancer and Preexisting Autoimmune Disorders

2018 ◽  
Vol 36 (19) ◽  
pp. 1905-1912 ◽  
Author(s):  
Giulia C. Leonardi ◽  
Justin F. Gainor ◽  
Mehmet Altan ◽  
Sasha Kravets ◽  
Suzanne E. Dahlberg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Systemic Corticosteroids ◽  
Programmed Death ◽  
Number Of Patients

Purpose Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non–small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown. Methods As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions. Results We identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%. Conclusion In patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.

scholarly journals Clinical impact of low serum free T4 in patients with non-small cell lung cancer treated with nivolumab

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tomoko Yamamoto Funazo ◽  
Takashi Nomizo ◽  
Hiroaki Ozasa ◽  
Takahiro Tsuji ◽  
Yuto Yasuda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nucleotide Polymorphisms ◽  
Small Cell Lung ◽  
Free T4 ◽  
Single Nucleotide ◽  
Programmed Death

AbstractNivolumab improves the prognosis of non-small cell lung cancer (NSCLC) but can cause immune-related adverse events (irAEs). Reports have indicated longer progression-free survivals (PFSs) in patients with irAEs than in those without irAEs. We reported associations between programmed death ligand-1 (PD-L1) single nucleotide polymorphisms (SNPs) and PFS after nivolumab treatment. We hypothesized that adverse events might be associated with the SNPs of PD-L1. We analyzed data from 111 patients with NSCLC treated with nivolumab. The response rate was 14%, and the median PFS was 68 days. We found patients with the adverse event of low free tetraiodothyronine (fT4) had significantly longer PFSs than those without low fT4 (not reached vs 67 days; hazard ratio [HR], 0.297; P = 0.010). Moreover, median overall survival was longer in patients with low fT4 than those without low fT4 (not reached vs 556 days, HR, 0.139; P = 0.020). Patients with the T allele of rs1411262 (P = 0.0073) and with the A allele of rs822339 (P = 0.0204) developed low fT4. Patients with the T/T genotype had longer PFSs than with those with the C/T and C/C genotypes of rs1411262 (165 vs. 67 days, HR, 1.65; P = 0.040), and those with the A/A genotype had longer PFSs than those with the A/G and G/G genotypes of rs822339 (182 vs. 67 days, HR, 1.76; P = 0.025). In the patients with advanced NSCLC, low fT4 after nivolumab treatment was associated with significantly longer PFSs. The SNPs of PD-L1 may be associated with the adverse events of nivolumab.

Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study

2017 ◽  
Vol 35 (34) ◽  
pp. 3823-3829 ◽  
Author(s):  
Patrick A. Ott ◽  
Elena Elez ◽  
Sandrine Hiret ◽  
Dong-Wan Kim ◽  
Anne Morosky ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
End Points ◽  
Phase Ib ◽  
Programmed Death ◽  
Extensive Stage

Purpose The safety and efficacy of pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), were assessed in patients with programmed death ligand 1 (PD-L1)–expressing extensive-stage small-cell lung cancer (SCLC) in the multicohort, phase Ib open-label KEYNOTE-028 study ( ClinicalTrials.gov identifier: NCT02054806). Methods Patients with SCLC received pembrolizumab 10 mg/kg every 2 weeks for 24 months or until disease progression or intolerable toxicity occurred. PD-L1 expression was assessed by immunohistochemistry. PD-L1–positive patients had membranous PD-L1 expression in ≥ 1% of tumor and associated inflammatory cells or positive staining in stroma. Response was assessed by investigator per Response Evaluation Criteria in Solid Tumors version 1.1 every 8 weeks for the first 6 months and every 12 weeks thereafter. Adverse events (AEs) were reported per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Primary end points were safety, tolerability, and objective response rate (ORR). Secondary end points included progression-free survival, overall survival, and duration of response. Results Twenty-four patients with PD-L1–expressing SCLC were enrolled and received at least one pembrolizumab dose. At the data cutoff date (June 20, 2016), the median follow-up duration was 9.8 months (range, 0.5 to 24 months). All 24 patients experienced AEs; the most common were asthenia (n = 7), fatigue (n = 7), and cough (n = 6). Two patients experienced grade 3 to 5 treatment-related AEs: one patient had elevated bilirubin, and one patient had asthenia, grade 5 colitis, and intestinal ischemia. One patient had a complete response, and seven patients had partial responses, resulting in an ORR of 33% (95% CI, 16% to 55%). Conclusion The safety of pembrolizumab was consistent with the known safety profile in other tumor types. Pembrolizumab demonstrated promising antitumor activity in patients with pretreated, PD-L1–expressing SCLC.

Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

2019 ◽  
Vol 19 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Bing-Di Yan ◽  
Xiao-Feng Cong ◽  
Sha-Sha Zhao ◽  
Meng Ren ◽  
Zi-Ling Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Specific Immunotherapy ◽  
Meta Analysis ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). </P><P> Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. </P><P> Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). </P><P> Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

440 Activity and safety of camrelizumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced non-small-cell lung cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A466-A466
Author(s):  
Guo Gui Sun ◽  
Jing Hao Jia ◽  
Peng Gao ◽  
Xue Min Yao ◽  
Ming Da Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Large Sample Size ◽  
Small Cell Lung ◽  
Previously Treated ◽  
Line Chemotherapy

BackgroundEffective options are limited for patients with non–small-cell lung cancer (NSCLC) whose disease progresses after first-line chemotherapy. Camrelizumab is a potent anti-PD-1 monoclonal antibody and has shown promising activity in NSCLC. We assessed the activity and safety of camrelizumab for patients with previously treated, advanced NSCLC patients with negative oncogenic drivers.MethodsPatients who progressed during or following platinum-based doublet chemotherapy were enrolled. All patients received camrelizumab(200 mg)every 3 weeks or in combination with chemotherapy until loss of clinical benefit. The primary endpoint was objective response rate (ORR), other endpoints included disease control rate (DCR), progression-free survival (PFS) and safety.ResultsBetween Aug 5, 2019, and Jun 19, 2020, we enrolled 29 patients, 25 patients were available evaluated, ORR and DCR was 36% (9/25) and 92% (23/25), respectively. 25 of 29 patients were still receiving the treatment, the median PFS was not yet achieved. Compared with those without reactive cutaneous capillary endothelial proliferation (RCCEP), patients with RCCEP had higher ORR (60% vs. 28.6%). Treatment-related adverse events (AEs) occurred in 69.0% of patients (all Grade), and the most common were RCCEP (37.9%), pneumonitis (6.9%), and chest congestion (6.9%). Treatment-related grade 3 to 4 adverse events occurred in 10.3% of patients.ConclusionsIn patients with previously treated advanced NSCLC, camrelizumab demonstrated improved ORR and DCR, compared with historical data of the 2nd line chemotherapy, with a manageable safety profile. While patients with RCCEP derived greater benefit from camrelizumab. Further studies are needed in large sample size trials.

scholarly journals Predictive value of 3′-deoxy-3′-18F-fluorothymidine PET in the early response to anti-programmed death-1 therapy in patients with advanced non-small cell lung cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e003079
Author(s):  
Masayuki Sato ◽  
Yukihiro Umeda ◽  
Tetsuya Tsujikawa ◽  
Tetsuya Mori ◽  
Miwa Morikawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Initiation ◽  
Early Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Flt Pet ◽  
Programmed Death ◽  
Programmed Death 1

BackgroundAnti-programmed death-1 (anti-PD-1) therapy has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). However, it is difficult to evaluate the early response to anti-PD-1 therapy. We determined whether changes in 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) PET parameters before and soon after treatment initiation predicted the therapeutic effect of anti-PD-1 antibody.MethodsTwenty-six patients with advanced NSCLC treated with anti-PD-1 antibody were enrolled prospectively and underwent 18F-FLT PET before and at 2 and 6 weeks after treatment initiation. Changes in maximal standardized uptake value (ΔSUVmax), proliferative tumor volume (ΔPTV) and total lesion proliferation (ΔTLP) of the lesions were calculated and evaluated for their associations with the clinical response to therapy.ResultsThe disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLP at 2 weeks, and decreased SUVmax, PTV, and TLP at 6 weeks, compared with those with PD, while three of eight (37.5%) patients who responded had increased TLP from baseline at 2 weeks (ie, pseudoprogression). Among the parameters that changed between baseline and 2 weeks, ΔPTV0-2 and ΔTLP0-2 had the highest accuracy (76.0%) to predict PD. Among the parameters that changed between baseline and 6 weeks, ΔSUVmax0-6, ΔPTV0-6 and ΔTLP0-6 had the highest accuracy (90.9%) to predict PD. ΔTLP0-2 (≥60%, HR 3.41, 95% CI 1.34–8.65, p=0.010) and ΔTLP0-6 (≥50%, HR 31.4, 95% CI 3.55 to 276.7, p=0.0019) were indicators of shorter progression-free survival.ConclusionsChanges in 18F-FLT PET parameters may have value as an early predictive biomarker for the response to anti-PD-1 therapy in patients with NSCLC. However, it should be noted that pseudoprogression was observed in 18F-FLT PET imaging at 2 weeks after treatment initiation.Trial registration numberjRCTs051180147.

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