scholarly journals Outcome of EGFR inhibitors treatment in advanced NSCLC patients, not enrolled in clinical trials

Neoplasma ◽  
2017 ◽  
Vol 64 (02) ◽  
pp. 253-261 ◽  
Author(s):  
M. Mencoboni ◽  
R. A. Filiberti ◽  
P. Taveggia ◽  
A. Bruzzone ◽  
A. Garuti ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Advanced Nsclc ◽  
Egfr Inhibitors ◽  
Nsclc Patients

Impact of rapid multigene assays with short turnaround time (TAT) on the development of precision medicine for non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9094-9094
Author(s):  
Shingo Matsumoto ◽  
Takaya Ikeda ◽  
Kiyotaka Yoh ◽  
Akira Sugimoto ◽  
Terufumi Kato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Precision Medicine ◽  
Targeted Therapies ◽  
Advanced Nsclc ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Gene Testing ◽  
Genomic Screening ◽  
Nsclc Patients

9094 Background: A variety of oncogene drivers have been identified in NSCLC and molecularly-stratified precision medicine has led to improved survival in advanced NSCLC. Next-generation sequencing (NGS)-based testing is utilized to detect actionable gene alterations; however, the TAT of NGS is often too long to translate into clinical decision making. Thus, rapid multi-gene testing alternatives are needed. Methods: A lung cancer genomic screening project (LC-SCRUM-Asia) capturing clinical outcome was established in 2013 to identify patients with oncogene drivers and to support the development of novel targeted therapies. Since February 2013 to May 2019 (LC-SCRUM-Asia 1st-phase), single gene testing and/or a targeted NGS assay, Oncomine Comprehensive Assay (OCA), were used for the genomic screening. Since June 2019 to December 2020 (2nd-phase), a multi-gene PCR assay (Amoy 9-in-1 test) and a rapid NGS assay (Genexus/Oncomine Precision Assay [OPA]) were also implemented as rapid multi-gene testing. Results: A total of 10667 Japanese NSCLC patients, including 6826 in the 1st-phase and 3841 in the 2nd-phase, were enrolled in the LC-SCRUM-Asia. Success rate for OCA: 93%, for 9-in-1 test: 98%, for Genexus/OPA: 96%. Median TAT for OCA: 21 days, for 9-in-1 test: 3 days, for Genexus/OPA: 4 days. The frequencies of genetic alterations detected in the 1st-/2nd-phase were EGFR: 17/24%, KRAS: 15/16%, HER2 ex20ins: 4/3%, ALK fusions: 3/3%, RET fusions: 3/2%, ROS1 fusions: 3/2%, MET ex14skip: 2/2%, BRAF V600E: 1/1%, NRG1 fusions: 0/0.2% and NTRK3 fusions: 0.05/0.04%. Overall percent agreement of 9-in-1 test compared with OCA for EGFR/KRAS/HER2/BRAF/MET/ALK/ROS1/RET/NTRK3 alterations was 98%, and that of OPA compared with OCA was 95%. The rate of patients who received targeted therapies as 1st-line treatment was significantly elevated in the 2nd-phase compared with the 1st-phase (510/3841 [13%] vs. 567/6826 [8%], p < 0.001). Through the genomic screening, 1410 (37%) and 1269 (18%) candidate patients for clinical trials of KRAS, HER2, BRAF, MET, ALK, ROS1, RET or TRK-targeted drugs were identified in the 2nd-phase and in the 1st-phase, respectively. The rate of patients who were actually enrolled into the genotype-matched clinical trials were also significantly higher in the 2nd-phase than in the 1st-phase (222 [6%] vs. 186 [3%], p < 0.001). In 1st-line treatments for advanced NSCLC patients, the median progression-free survival was 8.5 months (95% CI, 7.7−9.4) in the 2nd-phase (n = 1839) versus 6.1 months (95% CI, 5.9−6.3) in the 1st-phase (n = 4262) (p < 0.001). Conclusions: Both the 9-in-1 test and Genexus/OPA had short TATs (3−4 days), high success rates (96−98%) and good concordance (95−98%) compared with another NGS assay (OCA). These rapid multi-gene assays highly contributed to enabling precision medicine and the development of targeted therapies for advanced NSCLC.

Assessing the risk of serious adverse events (SAEs) and death in non-small cell lung cancer (NSCLC) trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21576-e21576
Author(s):  
Nirali Marvania ◽  
Abigail Sy Chan ◽  
Joseph Abraham ◽  
Kenneth David Miller
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Phase I ◽  
Fixed Effects ◽  
Advanced Nsclc ◽  
Critical Role ◽  
Morbidity And Mortality ◽  
Phase Iii ◽  
Phase Iii Trials ◽  
Nsclc Patients

e21576 Background: Lung cancer is a leading cause of morbidity and mortality despite advances in targeted therapy and immunotherapy. Clinical trials play a critical role in improving treatment options however, pose significant known and unknown risks. The purpose of this study was to analyze the risk of SAEs (Grade 3 and 4 toxicity) and deaths in advanced NSCLC patients participating in phase I/II and III clinical trials. Methods: A literature search using Clinicaltrials.gov was conducted to identify published phase I/II and III clinical trials in advanced NSCLC patients. The data extracted included study name, total number of participants, SAEs, and deaths attributable to a study drug. A fixed-effects model was implemented to estimate summary proportions of SAEs among participants. The Freeman-Tukey double arcsine transformation was applied to stabilize the variances of SAEs and mortality proportions. Results: We evaluated 112 studies, of which 87% were phase I/II, and 13% were phase III clinical trials. Study sample sizes ranged from 7 to 659 patients for phase I/II studies and from 186 to 1391 for phase III studies. 107 studies had SAEs while 5 phase I/II studies had no SAEs reported. The overall estimated percentage of SAEs was 39.5% (95% Confidence Interval, CI: 38.8%, 40.2%). The estimated percentages of patients with SAE in phase I/II and phase III trials were 40.9% (95%CI: 39.8%, 42.0%) and 38.7% (95%CI: 37.8%, 39.6%), respectively (p = 0.001). The estimated percentages of deaths among patients were 1.1% (95%CI: 0.90%, 1.3%) overall, 1.1% (95%CI: 0.7%, 1.5%) in phase I/II trials and 1.7% (95%CI: 1.5%, 2.0%) in phase III trials. The difference in mortality between phase I/II and phase III trials was not statistically significant (p = 0.408). Conclusions: Patients with advanced stages (III/IV) of NSCLC have a high risk of morbidity and mortality from their primary disease and also from their treatment. Our study demonstrated SAEs and toxic deaths attributable to the treatment of approximately 40% and 1%, respectively. Phase I/II trials patients are at a slightly higher risk of SAEs compared to patients participating in phase III trials, although the differences might not be clinically significant.

scholarly journals Immune Checkpoint Blockade for Advanced NSCLC: A New Landscape for Elderly Patients

2019 ◽  
Vol 20 (9) ◽  
pp. 2258 ◽  
Author(s):  
Fabio Perrotta ◽  
Danilo Rocco ◽  
Fabiana Vitiello ◽  
Raffaele De Palma ◽  
Germano Guerra ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Elderly Patients ◽  
Advanced Nsclc ◽  
Cell Activity ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints ◽  
Efficacy And Safety ◽  
Older Subjects ◽  
Nsclc Patients ◽  
Careful Assessment

The therapeutic scenario for elderly patients with advanced NSCLC has been limited to radiotherapy and chemotherapy. Recently, a novel therapeutic approach based on targeting the immune-checkpoints has showed noteworthy results in advanced NSCLC. PD1/PD-L1 pathway is co-opted by tumor cells through the expression of PD-L1 on the tumor cell surface and on cells within the microenvironment, leading to suppression of anti-tumor cytolytic T-cell activity by the tumor. The success of immune-checkpoints inhibitors in clinical trials led to rapid approval by the FDA and EMA. Currently, data regarding efficacy and safety of ICIs in older subjects is limited by the poor number of elderly recruited in clinical trials. Careful assessment and management of comorbidities is essential to achieve better outcomes and limit the immune related adverse events in elderly NSCLC patients.

scholarly journals EGFR Inhibitors Plus Bevacizumab are Superior Than EGFR Inhibitors Alone as First-Line Setting in Advanced NSCLC With EGFR Mutations and BIM Deletion Polymorphisms (BIM-CLICaP)

2021 ◽  
pp. 839-848
Author(s):  
Andrés F. Cardona ◽  
Camila Ordóñez-Reyes ◽  
Alejandro Ruiz-Patiño ◽  
Juan Esteban Garcia-Robledo ◽  
Lucia Zatarain Barron ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Overall Survival ◽  
Advanced Nsclc ◽  
Egfr Inhibitors ◽  
Egfr Mutations ◽  
First Line ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Nsclc Patients ◽  
Egfr Tkis

PURPOSE BIM activation is essential for epidermal growth factor receptor ( EGFR)-tyrosine kinase inhibitor (TKI)–triggered apoptosis in EGFR-mutant non–small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions ( BIMdel). MATERIALS AND METHODS A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups. RESULTS Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS. CONCLUSION EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.

Ligands of EGFR and the insulin-like growth factor family as serum biomarkers for response to EGFR-inhibitors in patients with advanced NSCLC

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8100-8100
Author(s):  
M. A. Vollebergh ◽  
I. Kappers ◽  
M. M. van den Heuvel ◽  
J. C. Buning-Kager ◽  
C. M. Korse ◽  
...  
Keyword(s):  
Overall Survival ◽  
Growth Factor ◽  
Proportional Hazards ◽  
Transforming Growth Factor ◽  
Advanced Nsclc ◽  
Egfr Inhibitors ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Transforming Growth Factor Α ◽  
Nsclc Patients

8100 Background: To determine whether concentrations of transforming growth factor α (TGFa), amphiregulin (ARG), both ligands of the epidermal growth factor receptor (EGFR), insulin-like growth factor 1(IGF1) or IGF-binding protein 3 (IGFBP3) measured in serum of advanced non-small cell lung cancer (NSCLC) patients are predictive of EGFR-inhibitors (EGFRi) response. Methods: We assessed serum levels of marker candidates using ELISA (TGA and ARG) and chemiluminescent (IGF1 and IGFBP3) assays. Sixty-one advanced NSCLC patients treated with EGFRi (gefitinib or erlotinib, >14 days) were matched for gender, age and histology to a control group of 63 EGFRi-untreated advanced NSCLC patients. We dichotomized marker levels at the 20th, 50th or 80th percentile and evaluated whether the effect of EGFRi treatment on overall survival (OS) differed by marker level based on multivariate proportional hazards regression with an interaction term. We adjusted for gender, smoking, stage, histology and prior chemotherapy. Results: While 6-months OS did not appreciably differ between 50 EGFRi treated and 50 control patients whose TGFa levels were below the 80th percentile (39% vs. 54%, multivariate HR 0.78, 95% CI 0.45–1.34, p=0.359), it was substantially worse for 11 EGFRi treated patients compared with 13 control patients whose TGFa levels were high (9% vs. 42%, multivariate HR 2.38, 95% CI 0.87–6.52, p=0.092). The difference of EGFRi effects by TGFa level was statistically significant (interaction p=0.033). There was no evidence that EGFRi treatment effects differed by levels of ARG, IGF1 and IGFBP3. Patients with high concentrations of IGFBP3 (above the median) had significantly longer OS than patients with low IGFBP3 concentrations, independent of treatment (HR 0.46, 95% CI 0.29–0.73, p=0.001). Conclusions: This is the first study in NSCLC patients of Caucasian origin in which serum concentrations of TGFa are predictive for EGFR-inhibitor response, suggesting this is a potential predictive marker for EGFRi treatment. Furthermore, we coincidentally found that levels of IGFBP3 are predictive for overall survival, indicating this might be a prognostic factor in advanced NSCLC patients. [Table: see text]

Safety and clinical efficacy of programmed cell death 1 antibodies (PD-1 Ab) in patients with advanced non-small cell lung cancer (NSCLC).

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 260-260
Author(s):  
Doran Ksienski ◽  
Elaine Wai ◽  
Nicole Croteau ◽  
Mary Lesperance
Keyword(s):  
Clinical Trials ◽  
Advanced Nsclc ◽  
Smoking Status ◽  
Multivariable Analysis ◽  
Physician Education ◽  
Kaplan Meier ◽  
Comorbidity Index ◽  
Cox Proportional Hazard Regression ◽  
Ecog Ps ◽  
Nsclc Patients

260 Background: In advanced NSCLC, clinical trials have shown significant benefits to pembrolizumab (P) and nivolumab (N). At BC Cancer, clinicians utilize protocol based algorithms to manage immune related adverse events (irAE). The incidence of irAE and efficacy of PD-1 Ab in everyday practice might differ from clinical trials. Methods: Advanced NSCLC patients (pts) treated with N or P between 11/2015 to 10/2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Gr, CTCAE v4.0) of irAE, were abstracted. Kaplan-Meier curves of median overall survival (OS) from initiation of PD-1 Ab were generated. Multivariable analysis (MVA) with 6-week landmark analysis was performed with Cox proportional hazard regression models. Results: Characteristics of cohort (230 N- and 41 P- treated): median age 64y (range 39-82), non-squamous histology 75%, ECOG PS > 1 at start of PD-1 Ab 31%, brain metastases (mets) 13%, liver mets 12%, and median Charlson Comorbidity Index (CCI) score 6. One hundred sixteen pts experienced 169 separate irAE: Gr1(74), Gr2 (68), Gr3(13), Gr4(10), Gr 5(4). Pneumonitis (14.6% vs. 4.8%, p = 0.041) and arthralgias (12.2% vs. 3.5%, p = 0.044) were more common in P than N. Steroids were administered to 25.2% of N pts and 19.5% of P pts (p = 0.557). Median follow-up from initiation of PD-1 Ab was 8.1months (range 0.1-33.9); median OS (95% CI) for N was 9.2 months (7.75-12.4) and for P was 13.5 months (10.6-not reached). 6-week landmark MVA for whole cohort revealed that male sex (p = 0.051), CCI≥3 (p < 0.001), ECOG PS > 1 (p < 0.001), liver mets (p = 0.017) and development of irAE > Gr2 versus no irAE (p = 0.036) were associated with decreased OS. Age, smoking status, histology, brain mets, EGFR status, irAE Gr 1/2 versus no irAE, and type of PD-1 Ab were not significant. Conclusions: Severe irAE were rare; pneumonitis and arthralgias were more common in P- than N- treated patients. The association with CCI, ECOG PS, and liver mets with decreased OS are consistent with literature. Association of severe irAE with shorter OS might reflect the need for improved physician education in irAE treatment algorithms.

Comparison of population characteristics, treatment modes, and clinical outcomes of patients with advanced non-small cell lung cancer in clinical trials and in the real world received PD-1/PD-L1 inhibitor.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18733-e18733
Author(s):  
Zhiyong Ma ◽  
Huijuan Wang ◽  
Chunhua Wei ◽  
Zhang guo Wei ◽  
Xiangtao Yan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Statistical Difference ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Population Characteristics ◽  
Small Cell Lung ◽  
The Real ◽  
Baseline Characteristics ◽  
Nsclc Patients

e18733 Background: Although PD-1/PD-L1 inhibitors have become the standard treatment for patients with advanced non-small cell lung cancer (NSCLC), data from clinical trials are difficult to be verified in the real world. This study aims to compare the differences in population characteristics, treatment modes and clinical outcomes of advanced NSCLC patients received PD-1/PD-L1 inhibitors between the real-world (RWS) and the clinical study (RCT). Methods: This study enrolled 305 advanced NSCLC patients who received at least one PD-1/PD-L1 inhibitor treatment selected in the Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital Information System and the Zero Krypton database during January 2016 to September 2019. The patients were divided into RWS group and RCT group. The PD-1/PD-L1 inhibitors included pembrolizumab, sintilizumab, nivolizumab, tislelizumab, carrelizumab, teriprizumab, durvalizumab and Atezolizumab. We performed paired analysis in clinical characteristics and treatment modes. Results: There were 155 cases in the RCT group and 150 cases in the RWS group. The RCT group consisted of higher proportion in male (79.4%) and squamous-carcinoma type (41.3%) than the RWS group, while more patients of brain metastasis (28%) and combination therapy (50.7%) in the RWS group. The ORRs were 42.4% and 20.6% respectively in the RCT and RWS groups receiving first-line treatment with PD-1/PD-L1 inhibitors, and the difference was statistically different. Moreover, the ORRs were 42.4% and 20.6% respectively in the RCT and RWS groups receiving PD-1/PD-L1 inhibitor as second-line treatment, without statistical difference. The progression-free survival (PFS) was 15.5 vs. 13.5 months in the RCT and RWS groups ( P= 0.91), and the median overall survival (OS) was 25.4 vs. 33.8 months respectively ( P= 0.24), with no statistical difference. After propensity match of baseline characteristics of the two groups of patients, it contained 108 patients in the RCT and RWS groups. The PFS was 13.3 vs. 13.3 months in the RCT and RWS groups ( P= 0.47), and the median OS was 21.1 vs. 23.2 months ( P= 0.58), with no statistical difference. Conclusions: Although more female, brain metastases and adenocarcinoma patients receiving PD-1/PD-L1 inhibitors in the real world, the clinical benefits were consistent with those in clinical trials. The results of propensity matching on the baseline characteristics of patients supported this conclusion.

Irreversible EGFR Inhibitors in the Treatment of Advanced NSCLC

2014 ◽  
Vol 20 (24) ◽  
pp. 3894-3900 ◽  
Author(s):  
Paolo Maione ◽  
Antonio Rossi ◽  
Marianna Bareschino ◽  
Paola Sacco ◽  
Clorinda Schettino ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Egfr Inhibitors
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