Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations
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ABSTRACT:
SUBMITTER: Jun S
PROVIDER: S-EPMC10670305 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn Canada, epidermal growth factor receptor (EGFR) inhibitor therapies in advanced non-small cell lung cancer (NSCLC) were initially approved regardless of EGFR status. The purpose of this study is to characterise the use of second or later-line erlotinib therapy in Ontario, Canada from 2007-2016, as well as evaluate the impact of erlotinib therapy on survival and emergency department (ED) visits in a real-world population.MethodsThis is a retrospective cohort study derived at ICES (formerly known as the Institute for Clinical and Evaluative Sciences) of advanced NSCLC patients diagnosed from 2007-2016 in Ontario, Canada, over the age of 65, who received at least one dose of first-line chemotherapy. The exposure of interest was receipt of second or later-line erlotinib. The primary outcome was the hazard ratio for mortality evaluated using a Cox proportional hazards model, and the secondary outcome, ED visits, was evaluated using a Poisson model.ResultsFirst-line chemotherapy was administered in 30.4% of stage IV NSCLC patients. Of these patients, 19.7% received second or later-line erlotinib. The proportion of patients prescribed second or later-line erlotinib decreased over the course of the study (P<0.0001). Unadjusted median overall survival in the entire cohort was 325 days (95% CI: 314-337 days), 513 days (95% CI: 485-539 days) in the erlotinib cohort, and 282 days (95% CI: 270-291 days) in the non-erlotinib cohort. Despite this, the adjusted hazard ratio for death was 1.89 (95% CI: 1.73-2.07, P<0.0001) for patients on erlotinib. Patients receiving erlotinib also had a marginally higher relative rates of ED visits with an adjusted relative risk of 1.10 (95% CI: 1.02-1.19, P=0.013).ConclusionsThis study highlights the importance of using EGFR targeted treatments in NSCLC patients with a predictive biomarker, and suggests that treatment with erlotinib therapy is unlikely to benefit unselected patients with advanced NSCLC.
| S-EPMC8482335 | biostudies-literature
Project description:BackgroundWe conducted a post-marketing surveillance study to evaluate the clinical tolerability and safety of atezolizumab in Japanese patients with non-small-cell lung cancer (NSCLC).MethodsThis prospective, observational post-marketing cohort study was conducted in NSCLC patients who received atezolizumab 1200 mg every 3 weeks at 770 facilities in Japan between April 18, 2018, and March 31, 2020 (study number UMIN000031978). Case report forms were completed, recording patient characteristics, treatment details, adverse events, adverse drug reactions (ADRs), their severity, onset and outcomes. Follow-up was for 12 months or until atezolizumab discontinuation.ResultsOverall, 2570 patients were included, median age was 69.0 years, and 69.9% were males. ADRs were reported in 29.1% of patients, most commonly pyrexia (4.2%). Grade ≥ 3 ADRs occurred in 9.7% of patients aged <75 and 9.7% of those aged ≥75 years. The incidence of Grade ≥ 3 ADRs was not affected by the number of lines of previous treatment or the presence or history of an autoimmune disorder. Immune-related ADRs of interest that occurred in >1% of patients were interstitial lung disease (ILD; 4.4%), endocrine disorder (4.3%), and hepatic dysfunction (2.8%). ILD was significantly more common in patients with a history of, or concurrent, ILD versus those without (P ≤ 0.001). Risk factors of Grade ≥ 3 ADRs were a history of, or concurrent, ILD. Grade 5 ADRs occurred in 35 patients, 11 of whom had concurrent ILD.ConclusionsThis large cohort study confirmed the clinical tolerability of atezolizumab in a real-world group of Japanese patients with NSCLC.
| S-EPMC9157296 | biostudies-literature
Project description:BackgroundLazertinib is an oral, third-generation EGFR-TKI, which specifically targets the EGFR T790M mutation along with activating mutations Ex19del and L858R. More real-world data are needed to evaluate its efficacy and safety in treating locally advanced and metastatic non-small cell lung cancer (NSCLC) following prior EGFR TKI treatment.MethodsThis multicenter retrospective study was conducted at seven university hospitals affiliated to the Catholic Medical Center (CMC) in Korea. A clinical data warehouse (CDW) platform was used to access and extract information.ResultsA total of 48 patients were assessed. The majority were female (75%) and diagnosed with adenocarcinoma (95.8%). All patients had the EGFR mutation at diagnosis, 27 (56.3%) had the exon 19 deletion, 20 (41.7%) had the L858R mutation, and one (2.0%) had the exon 18 mutation. The median progression-free survival (PFS) was 15.4 months. At 6, 12, and 18 months, PFS rates were 79.1%, 53.6%, and 27.3%, respectively. When PFS was analyzed by prior TKI duration (<18 months vs. >18 months), significant differences were noted at the 6 and 9-month mark (p = 0.013 and p = 0.010, respectively). In multivariate analysis for PFS, only prior TKI duration and ECOG score showed statistical significance (p = 0.026 and p = 0.049, respectively). In the multivariate analysis for OS, ECOG score showed statistical significance (p = 0.006). Among 48 patients, 34 (70.8%) experienced adverse events (AEs) related to lazertinib. The most frequent AEs were skin reaction (29.8%), diarrhea (21.3%), and peripheral neuropathy (20.8%).ConclusionsThe results suggest that lazertinib is effective in second or more line settings, with tolerable safety profile. More patient data are necessary to find possible prognostic markers associated with patient outcome.
| S-EPMC11219289 | biostudies-literature
Project description:BackgroundTaxane chemotherapy represents the standard of care in the second-line setting for non-small cell lung cancer (NSCLC) patients, but immunotherapy agents pose great challenges. Whether immunotherapy/chemotherapy alone or combination therapy has more benefits remains controversial. In this study, we provided comparisons to integrate the efficacy of immunotherapy and taxane chemotherapy as second- or later-line treatments in advanced NSCLC.MethodsPubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to September 1, 2020. Randomized controlled trials comparing immunotherapy and taxane chemotherapy were enrolled in the Bayesian network analysis. Overall survival (OS) and progression-free survival (PFS) with hazard ratios (HRs) were investigated.ResultsEight trials in 13 studies with 4398 patients comparing seven treatments were identified. Pembrolizumab 10 mg/kg was associated with the best improved OS, with significant differences versus docetaxel (HR 0.81, 95% credible interval [CrI] 0.74-0.88), avelumab (HR 0.84, 95% CrI 0.75-0.95), and pembrolizumab 200 mg plus docetaxel (HR 0.75, 95% CrI 0.56-1.00). Although pembrolizumab 200 mg plus docetaxel ranked the last in terms of OS, the combination therapy showed the most favorable PFS. Additionally, the anti-programmed death-ligand 1 (PD-L1) agent, avelumab, was associated with the least improvement in PFS.ConclusionAs second- or later-line therapeutic strategies, pembrolizumab 10 mg/kg provided the largest OS benefits and pembrolizumab 200 mg plus docetaxel improved PFS to the greatest extent. Considering that immunotherapy has been recommended to the first-line setting of NSCLC, advanced patients who have not received immunotherapy previously might be the suitable population for our findings.
| S-EPMC9666094 | biostudies-literature
Project description:ObjectiveDacomitinib has been approved for the first-line treatment of non-small cell lung cancer (NSCLC) carrying classical epidermal growth factor receptor (EGFR) mutations; however, real-world data on its later-line application are lacking.Materials and methodsPatients' data were retrospectively collected from the Chinese National Cancer Center and the PLA hospital between August 2019 and August 2021. Kaplan-Meier method and Log-rank test were utilized to assess progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analysis was conducted to determine prognostic indicators.ResultsIn total, 56 NSCLC patients harboring EGFR mutations treated with later-line single dacomitinib or combinatory dacomitinib were enrolled. A total of 53 patients (94.6%) had treatment-related adverse events; eight patients (14.3%) had grade 3 or 4 events. Among 49 evaluable patients, 26.5% (13 patients) had a confirmed partial response and 73.5% (36 patients) had disease control; the median duration of follow-up was 9.6 months (95% confidence interval [CI], 8.4-10.8 months), the median progression-free survival was 5.4 months (95% CI, 3.5-7.3 months), and the half-year, 1-year, and 2-year OS rate were 79.2%, 70.6%, and 64.1%, respectively. Univariate analysis suggested that smoking, line of dacomitinib, and interval between last EGFR-tyrosine kinase inhibitor (TKI) and dacomitinib were associated with PFS and OS; chemotherapy between last EGFR-TKI and dacomitinib, and EGFR-TKI generation followed by dacomitinib were respectively associated with PFS and OS; multivariate analysis indicated chemotherapy between last EGFR-TKI and dacomitinib negatively affect PFS, and smoking and third-generation EGFR-TKI followed by dacomitinib negatively affect OS.ConclusionsThis real-world study has shown that dacomitinib is active and well-tolerated in NSCLC patients harboring different EGFR mutations in later-line settings, even for those with brain metastases. Patients who benefited more from the first TKI were more likely to benefit from dacomitinib, and earlier application of dacomitinib after front-line TKI resistance may be considered.
| S-EPMC8855913 | biostudies-literature
Project description:ObjectiveThis study sought to assess the efficacy and safety of immunotherapy combined with single-agent chemotherapy as a second- or later-line setting for metastatic non-small cell lung cancer (NSCLC) and to provide clinical evidence for this treatment regimen. The predictive value of extracellular vesicle (EV) membrane proteins was explored in patients who underwent this treatment.MethodsClinical data from patients diagnosed with metastatic NSCLC who received immunotherapy plus single-agent chemotherapy as a second- or later-line setting were retrospectively collected between March 2019 and January 2022. A total of 30 patients met the inclusion criteria, and all were pathologically confirmed to have NSCLC. Short-term efficacy, progression-free survival (PFS), EV markers for response prediction, and adverse events were assessed.ResultsEfficacy data were available for all 30 patients and included a partial response in 5 patients, stable disease in 18 patients, and disease progression in 7 patients. The objective response rate was 16.7%, the disease control rate was 76.7%, and the median PFS was 3.2 months. Univariate analysis showed that PFS was not associated with sex, age, smoking status, treatment lines, prior use of immunotherapy, or prior use of antiangiogenic drugs. The EV membrane proteins MET proto-oncogene, receptor tyrosine kinase (c-MET), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptor 2 (VEGFR2) at baseline were associated with poor prognosis and correlated with the efficacy of immunotherapy plus chemotherapy. According to the receiver operating characteristics and Kaplan-Meier curve analyses, patients with high c-MET, EGFR, and VEGFR2 expression at baseline had significantly shorter PFS than those with low expression. In addition, VEGFR2 expression was increased after combined immunotherapy in responders, which was decreased in non-responders. The most common grade 2 or higher adverse events were neutropenia, gastrointestinal reactions, and thyroid dysfunction, all of which were tolerated.ConclusionsImmunotherapy plus single-agent chemotherapy as a second- or later-line treatment is safe, effective, and tolerable for metastatic NSCLC. EV markers can be used as predictive markers of efficacy in patients with metastatic NSCLC treated with immunotherapy plus chemotherapy to help monitor treatment efficacy and guide treatment decisions.
| S-EPMC10547148 | biostudies-literature
Project description:BackgroundLimited treatment options exist for relapsed advanced lung squamous cell carcinoma (SCC), leading to poor outcomes compared with adenocarcinoma. This study aimed to investigate the efficacy of second-line afatinib versus chemotherapy in patients with advanced lung SCC who progressed after first-line chemotherapy.MethodsIn this retrospective, multisite cohort study, we recruited patients with initial locally advanced or metastatic lung SCC from four institutes in Taiwan between June 2014 and October 2020. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and overall survival (OS).ResultsThe present study enrolled 108 patients: 19 received second-line afatinib, and 89 received second-line chemotherapy. The median ages were 71 and 67 years, respectively. PFS was significantly longer among patients who received afatinib than among those who received chemotherapy (median 4.7 months [95% confidence interval (CI), 0.1-7.5] vs. 2.6 months [95% CI, 0.9-6.7]; hazard ratio (HR) 0.53 [95% CI 0.32-0.88], p = 0.013). Compared with the chemotherapy group, OS was longer in the afatinib group but did not reach significance (median 16.0 months [95% CI, 6.1-22.0] vs. 12.3 months [6.2-33.9]; HR 0.65 [95% CI 0.38-1.11], p = 0.112).ConclusionsAfatinib offered a longer PFS and comparable OS to chemotherapy in advanced lung SCC patients in a real-world setting, it may be considered as a 2nd line alternative treatment choice for immunotherapy unfit advanced lung SCC patients.
| S-EPMC8594240 | biostudies-literature
Project description:BackgroundNon-small cell lung cancer (NSCLC) in never-smokers (NS) is vastly different from those with a smoking history in terms of etiology, driver mutations, and immunotherapy responsiveness. This study compares the real-world overall survival (OS) of NSCLC patients by smoking history and mutation status.MethodsThe study included 30,310 advanced or metastatic NSCLC patients in the Flatiron Health EHR-derived database who received biomarker testing results (EGFR, ALK, ROS1, and BRAF), and initiated therapy between 2011 and 2017, with follow up through June 2018. OS by smoking and driver mutation groups was summarized via Kaplan-Meier survival estimates, and compared in the context of a multivariate Cox proportional hazard model.ResultsOS differed by smoking and driver-mutation categories (adjusted and stratified P< .001). The median OS for wild-type (WT) smoking patients was 9.6 months, for mutated (MT) smokers was 19.4 months (adjusted and stratified hazard ratio [HR] relative to WT smokers 0.65; 95% CI 0.60-0.71), for WT NS was 15.1 months (HR 0.78; 95% CI 0.73-0.83 relative to WT smokers), and for MT NS was 25.5 months (HR 0.52; 95% CI 0.48-0.58 relative to WT smokers).ConclusionNS with NSCLC survived longer than those with smoking history, in both groups of WT and mutation-positive patients. Findings highlight that in NSCLC patients, a history of never smoking may have similar effect on hazard of death as the presence of an actionable mutation. Taken together, differences in heredity, mutations, and biologic history suggest that NS lung cancer is a distinct clinical entity and must be managed accordingly.
| S-EPMC8310892 | biostudies-literature
Project description:BackgroundNeoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.MethodsTumor molecular profiles were obtained from patients with stage I-IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF was defined as any progression of primary lung cancer after neoadjuvant ICI therapy in patients without surgery, radiographic and/or biopsy-proven primary lung cancer recurrence after surgery, or death from possibly treatment-related complications or from primary lung cancer since randomization. Tumors with AGAs (n=12) were compared with tumors without AGAs and non-profiled squamous cell carcinomas (non-AGAs+NP SCC, n=20).ResultsWith a median follow-up of 60.2 months, the overall TF rate was 34.1% (15/44). Tumor molecular profiling was retrospectively obtained in 47.7% (21/44) of patients and select AGAs were identified in 12 patients: 5 epidermal growth factor receptor (EGFR), 2 KRAS, 1 ERBB2, and 1 BRAF mutations, 2 anaplastic lymphoma kinase (ALK) and 1 RET fusions. The median time to TF in patients with AGAs was 24.7 months (95% CI: 12.6 to 40.4), compared with not reached (95% CI: not evaluable (NE)-NE) in the non-AGAs+NP SCC group. The TF risk was higher in AGAs (HR: 5.51, 95% CI: 1.68 to 18.1), and lower in former/current smokers (HR: 0.24, 95% CI: 0.08 to 0.75). The odds of major pathological response were 4.71 (95% CI: 0.49 to 45.2) times higher in the non-AGAs+NP SCC group, and the median percentage of residual viable tumor was 72.5% in AGAs compared with 33.0% in non-AGS+NP SCC tumors.ConclusionsPatients with NSCLC harboring select AGAs, including EGFR and ALK alterations, have a higher risk for TF, shorter median time to TF, and diminished pathological regression after neoadjuvant ICIs. The suboptimal efficacy of neoadjuvant chemotherapy-sparing, ICI-based regimens in this patient subset underscores the importance of tumor molecular testing prior to initiation of neoadjuvant ICI therapy in patients with resectable NSCLC.
| S-EPMC11499765 | biostudies-literature
Project description:BackgroundIn the ATLANTIS study, second-line lurbinectedin/doxorubicin did not improve overall survival (OS), however patients with a chemotherapy-free interval (CTFI) of ≥180 days had an improved progression free survival (PFS). The objective of this retrospective study was to identify the proportion of real-world small cell lung cancer (SCLC) patients who are suitable for lurbinectedin-based therapy based on these criteria.MethodsA retrospective study of all SCLC referred to BC Cancer between 2012 and 2017 was conducted. Patient demographics, staging, treatment, and survival data were collected retrospectively. Baseline characteristics were compared using descriptive statistics. OS was calculated using Kaplan-Meier curves. Statistically significant p-value was <0.05.ResultsA total of 1048 patients were identified. Baseline characteristics: median age 68 years, 47% male, 61% current smoking status, 68% extensive disease. Best supportive care was received by 22%. First-line systemic therapy was platinum doublet for 71% of the population. Second-line systemic therapy was delivered to 22%. Of the 219 patients who received second-line systemic therapy after platinum doublet, 183 patients had a CTFI of ≥90 days and 107 patients had a CTFI of ≥180 days. Patients originally treated as limited stage disease, received platinum doublet as second line, received thoracic radiation (RT) or prophylactic cranial irradiation (PCI) were more likely to have a CTFI of ≥90 and ≥180 days.ConclusionIn our real-world SCLC population, only 21% of the SCLC population received second-line therapy after platinum doublet with 17% achieving CTFI of ≥90 days and 10% CTFI of ≥180 days. Based on this retrospective review, only a small fraction of platinum-treated patients would be preferentially offered lurbinectedin in the second-line setting.
| S-EPMC9776936 | biostudies-literature