scholarly journals Immune-Related Adverse Events Are Associated With Clinical Benefit in Patients With Non-Small-Cell Lung Cancer Treated With Immunotherapy Plus Chemotherapy: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Kenji Morimoto ◽  
Tadaaki Yamada ◽  
Chieko Takumi ◽  
Yuri Ogura ◽  
Takayuki Takeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Confidence Interval ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Hazard Ratio ◽  
Small Cell Lung

BackgroundThe immunotherapy plus chemotherapy combination is one of the most promising treatments in advanced non-small-cell lung cancer (NSCLC). Immunotherapy often causes immune-related adverse events (irAEs), which have been reported to be associated with the good clinical outcomes. However, the effects of immunotherapy plus chemotherapy remain unknown. In this study, we investigated the association between irAEs caused by immunotherapy plus chemotherapy and clinical efficacy in patients with advanced NSCLC.Materials and MethodsWe retrospectively analyzed the data of patients with advanced NSCLC, who received a combination of immunotherapy plus chemotherapy at six institutions in Japan between January 2019 and September 2019. We examined the effect of irAEs on various clinical outcomes.ResultsWe included 70 patients with advanced NSCLC. Patients were divided into two groups: patients with irAEs and patients without irAEs. Patients with irAEs had significantly longer progression-free survival than those without irAEs on univariate (hazard ratio 0.53, 95% confidence interval 0.30–0.93, p = 0.026) and multivariate (hazard ratio 0.53, 95% confidence interval 0.29–0.97, p = 0.041) analyses. In addition, patients with grade 1–2 irAEs (mild irAEs) had significantly longer progression-free and overall survival than those with grade 3-5 irAEs (severe irAEs) or without irAEs on univariate (398 days versus 189 days, respectively; p = 0.0061) and multivariate (not reached versus 412 days, respectively; p = 0.021) analyses.ConclusionPatients with NSCLC who experienced mild irAEs showed better response to treatment with immunotherapy plus chemotherapy than those with severe irAEs or without irAEs. Further large-scale research is warranted to confirm these 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 Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-IIIA Non–Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase III Trial

2015 ◽  
Vol 33 (34) ◽  
pp. 4007-4014 ◽  
Author(s):  
Karen Kelly ◽  
Nasser K. Altorki ◽  
Wilfried E.E. Eberhardt ◽  
Mary E.R. O'Brien ◽  
David R. Spigel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Double Blind ◽  
Egfr Amplification

Purpose Epidermal growth factor receptor (EGFR) –tyrosine kinase inhibitors have proven efficacy in advanced non–small-cell lung cancer (NSCLC). We hypothesized that erlotinib would be efficacious in the adjuvant setting. Patients and Methods An international randomized, double-blind, placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization. Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years. Stratification factors were stage, histology, previous adjuvant chemotherapy, smoking status, EGFR amplification status, and country. The primary end point was disease-free survival (DFS); key secondary end points were overall survival (OS) and DFS and OS in patients whose tumors had EGFR-activating mutations (EGFRm-positive). Results A total of 973 patients were randomly assigned (November 26, 2007, to July 7, 2010). There was no statistically significant difference in DFS (median, 50.5 months for erlotinib and 48.2 months for placebo; hazard ratio, 0.90; 95% CI, 0.74 to 1.10; P = .324). Among the 161 patients (16.5%) in the EGFRm-positive subgroup, DFS favored erlotinib (median, 46.4 v 28.5 months; hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .039), but this was not statistically significant because of the hierarchical testing procedure. OS data are immature. Rash and diarrhea were common adverse events occurring in 528 (86.4%) and 319 (52.2%) patients treated with erlotinib, respectively, versus 110 (32.1%) and 54 (15.7%) patients receiving placebo. The most common grade 3 adverse events in patients treated with erlotinib were rash (22.3%) and diarrhea (6.2%). Conclusion Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup. Further evaluation of erlotinib is warranted in the EGFRm-positive subgroup.

Adjuvant chemotherapy for elderly patients with non-small-cell lung cancer

2017 ◽  
Vol 25 (5) ◽  
pp. 371-377 ◽  
Author(s):  
Keiji Yamanashi ◽  
Norihito Okumura ◽  
Yoshiharu Yamamoto ◽  
Ayuko Takahashi ◽  
Takashi Nakashima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Confidence Interval ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Hazard Ratio ◽  
Small Cell Lung ◽  
Free Survival ◽  
Stage Ib

Background Adjuvant chemotherapy after complete surgical resection is currently the standard of care for patients with stage IB, II, or IIIA non-small-cell lung cancer. However, the generalizability of this treatment to elderly patients is controversial. We investigated the effects of adjuvant chemotherapy in patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer. Methods We retrospectively analyzed 246 consecutive patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer who underwent standard lung cancer surgery between January 2001 and December 2015. They were divided into 102 who had adjuvant chemotherapy and 144 who had none (control group). The outcomes were compared between the two groups, and prognostic factors were evaluated. Results Relapse-free survival and overall survival were significantly shorter in the control group than the chemotherapy group ( p = 0.006 and p = 0.008, respectively). In multivariable analyses, adjuvant chemotherapy was found to be an independent prognostic factor for relapse-free survival and overall survival (hazard ratio = 0.594, 95% confidence interval: 0.396–0.893, p = 0.012; and hazard ratio = 0.616, 95% confidence interval: 0.397–0.957, p = 0.031, respectively). After inverse-probability-of-treatment weighting adjustment using the propensity score for baseline characteristics, chemotherapy almost improved relapse-free survival and overall survival (hazard ratio = 0.652, 95% confidence interval: 0.433–0.981, p = 0.040; and hazard ratio = 0.657, 95% confidence interval: 0.429–1.004, p = 0.052, respectively). Conclusions Adjuvant chemotherapy improved the prognosis after standard lung cancer surgery in patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer.

scholarly journals Multiorgan Immune-Related Adverse Events During Treatment With Atezolizumab

2020 ◽  
Vol 18 (9) ◽  
pp. 1191-1199
Author(s):  
Ganessan Kichenadasse ◽  
John O. Miners ◽  
Arduino A. Mangoni ◽  
Andrew Rowland ◽  
Ashley M. Hopkins ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Index ◽  
Small Cell ◽  
Hazard Ratio ◽  
Small Cell Lung ◽  
Organ Specific

Background: Immune-related adverse events (irAEs) are known to occur in patients with cancer who are treated with immune checkpoint inhibitors. However, limited literature exists on the incidence, time of onset, and risk factors for irAEs, particularly those affecting multiple organs, associated with anti–PD-L1 inhibitors. Methods: A post hoc pooled analysis was conducted using individual patient data from atezolizumab monotherapy arms of 4 non–small cell lung cancer clinical trials. Incidence, clinical patterns, outcomes, and risk factors were investigated of selected organ-specific and multiorgan irAEs during treatment using the anti–PD-L1 inhibitor atezolizumab. Results: From a total of 1,548 patients, 730 irAE episodes were reported in 424 patients (27%). Skin irAEs were the most common (42%), followed by laboratory abnormalities (27%) and endocrine (11.6%), neurologic (7.6%), and pulmonary (6.2%) irAEs. A total of 84 patients (5.4%) had multiorgan irAEs, 70 had 2, 13 had 3, and 1 had 4 different organs affected. “Skin plus” or “laboratory plus” were the most common irAE multiorgan clusters. Patients with multiorgan irAEs were more likely to be white and have a good performance status, a lower baseline neutrophil-lymphocyte ratio, and a good or intermediate lung immune prognostic index score. Multiorgan irAEs were also associated with improved overall survival (hazard ratio, 0.47; 95% CI, 0.28–0.78; P<.0001) but not with progression-free survival (hazard ratio, 0.92; 95% CI, 0.62–1.35; P=.74) compared with the cohort with no irAEs. Conclusions: Multiorgan irAEs occurred in 5.4% of patients treated with atezolizumab in non–small cell lung cancer trials. Future trials should consider routine reporting of data on multiorgan toxicities in addition to organ-specific toxicities.

scholarly journals Predictive and prognostic value of serum periostin in advanced non–small cell lung cancer patients receiving chemotherapy

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769836 ◽  
Author(s):  
Yan Zhang ◽  
Dongmei Yuan ◽  
Yanwen Yao ◽  
Wenkui Sun ◽  
Yi Shi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Confidence Interval ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Hazard Ratio ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Serum Periostin

Periostin is an extracellular matrix protein involved in tumorigenesis and metastasis. However, the role of serum periostin as a surrogate marker for treatment efficacy is still unknown. In 122 advanced non–small cell lung cancer cases, 37 patients with benign lung disease and 40 healthy controls, serum periostin was measured by enzyme-linked immunosorbent assays. The associations of serum periostin levels with the clinic-pathological parameters, chemotherapy response, and clinical outcomes of non–small cell lung cancer patients were analyzed. Serum periostin levels were significantly higher in non–small cell lung cancer patients, and it was related significantly to bone metastasis ( p = 0.021). Serum periostin of 65 non–small cell lung cancer patients were detected before and after two cycles of chemotherapy. The patients with and without periostin response had significant difference in objective response to chemotherapy ( p = 0.001). For the 122 non–small cell lung cancer patients, the median progression-free survival was 5 months. In a multivariate analysis, performance status (hazard ratio, 1.71; 95% confidence interval, 1.10–2.67), baseline periostin (hazard ratio, 1.01; 95% confidence interval, 1.00–1.01), and periostin response (hazard ratio, 0.50; 95% confidence interval, 0.29–0.86) were significantly correlated with prognosis. In conclusion, serum periostin was elevated in advanced non–small cell lung cancer patients. Baseline periostin and periostin responses appeared to be reliable surrogate markers to predict chemotherapy response and survival in patients with advanced non–small cell lung cancer.

Meta-Analysis of Randomized Clinical Trials Comparing Cisplatin to Carboplatin in Patients With Advanced Non–Small-Cell Lung Cancer

2004 ◽  
Vol 22 (19) ◽  
pp. 3852-3859 ◽  
Author(s):  
Katsuyuki Hotta ◽  
Keitaro Matsuo ◽  
Hiroshi Ueoka ◽  
Katsuyuki Kiura ◽  
Masahiro Tabata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Combination Chemotherapy ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Hazard Ratio ◽  
Survival Advantage ◽  
Small Cell Lung

Purpose It remains undetermined whether cisplatin and carboplatin are equally effective for advanced non–small-cell lung cancer (NSCLC). We therefore did a meta-analysis of trials that compared cisplatin-based chemotherapy with carboplatin-based chemotherapy. Methods We performed a literature search to identify trials that had investigated the substitution of carboplatin for cisplatin in the treatment of advanced NSCLC. We evaluated these trials for inclusion, rated methodologic quality, and abstracted relevant data. Results Of 1,191 reports, eight trials (2,948 patients) were identified, five of which investigated drug regimens containing platinum plus a new agent. Cisplatin-based chemotherapy produced a higher response rate, but the survival advantage was not significant (hazard ratio = 1.050; 95% CI, 0.907 to 1.216; P = .515). Subgroup analysis revealed that combination chemotherapy consisting of cisplatin plus a new agent yields 11% longer survival than carboplatin plus the same new agent (hazard ratio = 1.106; 95% CI, 1.005 to 1.218; P = .039). Patients on cisplatin-based chemotherapy frequently developed nausea and vomiting; thrombocytopenia was more frequent during carboplatin-based chemotherapy. No significant difference in treatment-related mortality was observed. Conclusion We found that combination chemotherapy consisting of cisplatin plus a new agent yields a substantial survival advantage compared with carboplatin plus a new agent in patients with advanced NSCLC, although we failed to find any survival difference in an analysis that included both new and old agents. The strength of our conclusion is limited because we used abstracted data, and careful interpretation is thus required. Nevertheless, our results raise a critical point that needs to be evaluated in future studies.

scholarly journals CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stanley I. Gutiontov ◽  
William Tyler Turchan ◽  
Liam F. Spurr ◽  
Sherin J. Rouhani ◽  
Carolina Soto Chervin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Loss Of Function ◽  
Small Cell Lung

AbstractImmune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02–2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21–3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

scholarly journals Dosimetry, Efficacy, Safety, and Cost-Effectiveness of Proton Therapy for Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4545
Author(s):  
Bin Qiu ◽  
Yu Men ◽  
Junjie Wang ◽  
Zhouguang Hui
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Proton Therapy ◽  
Advanced Nsclc ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung

Non-small cell lung cancer (NSCLC) is the most common malignancy which requires radiotherapy (RT) as an important part of its multimodality treatment. With the advent of the novel irradiation technique, the clinical outcome of NSCLC patients who receive RT has been dramatically improved. The emergence of proton therapy, which allows for a sharper dose of build-up and drop-off compared to photon therapy, has potentially improved clinical outcomes of NSCLC. Dosimetry studies have indicated that proton therapy can significantly reduce the doses for normal organs, especially the lung, heart, and esophagus while maintaining similar robust target volume coverage in both early and advanced NSCLC compared with photon therapy. However, to date, most studies have been single-arm and concluded no significant changes in the efficacy for early-stage NSCLC by proton therapy over stereotactic body radiation therapy (SBRT). The results of proton therapy for advanced NSCLC in these studies were promising, with improved clinical outcomes and reduced toxicities compared with historical photon therapy data. However, these studies were also mainly single-arm and lacked a direct comparison between the two therapies. Currently, there is much emerging evidence focusing on dosimetry, efficacy, safety, and cost-effectiveness of proton therapy for NSCLC that has been published, however, a comprehensive review comparing these therapies is, to date, lacking. Thus, this review focuses on these aspects of proton therapy for NSCLC.

Association between immune-related adverse events and clinical outcomes to PD-1/PD-L1 blockade in small cell lung cancer

2020 ◽  
pp. 100092
Author(s):  
Biagio Ricciuti ◽  
Abdul Rafeh Naqash ◽  
Jarushka Naidoo ◽  
Kartik Sehgal ◽  
Adam Miller ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung
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