Real-world evidence: Molecular subtype and its prognostic implications of Lung-molGPA in EGFR-mutated adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21621-e21621
Author(s):  
Feng-Che Kuan ◽  
Chung-Sheng Shi ◽  
Wei-Hsun Yang ◽  
Hung-Yi Lai ◽  
Chun-Chieh Huang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Egfr Mutations ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Real World Evidence ◽  
Prognostic Implications ◽  
Egfr Mutated ◽  
Exon 19

e21621 Background: EGFR mutations are heterogenous but all carry the same weight in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Methods: Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 256 patients were included with a median overall survival (OS) of 17.2months. Patients with Lung-molGPA scores of 1, 1.5-2.0, 2.5-3.0, and 3.5-4.0 had median OS of 5.9,11.5, 17.2, and 23.4months, respectively (p < 0.001). In multivariate analysis of OS, only age (³70 versus < 70 years, HR:1.71, 95% CI:1.25-2.35, p < 0.001), KPS ( < 70 versus ³70, HR:1.71, 95% CI:1.26-2.31, p < 0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p = 0.037) remained statistically significant. In patients with a Lung-molGPA score £2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.9vs 12.8vs 4.5months, p = 0.021) and prognostic implications (Leu858Arg versus exon 19 deletions, HR: 1.85, 95% CI: 1.20-2.84, p = 0.005; other versus exon 19 deletions, HR:2.18, 95% CI:1.11-4.26, p = 0.023). Conclusions: Different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

scholarly journals Title: Lung-molGPA in EGFR-mutated Adenocarcinoma: Prognostic Implications of Molecular Subtypes and Targeted Therapies

2020 ◽  
Author(s):  
Feng-Che Kuan ◽  
Chung-Sheng Shi ◽  
Wei-Hsun Yang ◽  
Meng-Hung Lin ◽  
Hung-Yi Lai ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Molecular Subtypes ◽  
Egfr Mutations ◽  
Rare Mutations ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Cox Proportional Hazard Models ◽  
Prognostic Implications ◽  
Egfr Mutated ◽  
Exon 19

EGFR mutations are heterogenous but all carry the same weighting in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 256 patients were included with a median overall survival (OS) of 17.2 months. In multivariate analysis of OS, only age (70 versus &amp;lt;70 years, HR:1.71, 95% CI:1.25-2.35, p&amp;lt;0.001), KPS (&amp;lt;70 versus 70, HR:1.71, 95% CI:1.26-2.31, p&amp;lt;0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p=0.037) remained statistically significant. In patients with a Lung-molGPA score 2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.8 vs 12.4 vs 12.1 months, p=0.021). In conclusion, different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

Real-world outcome analysis of EGFR-mutated lung adenocarcinoma with brain metastases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13588-e13588
Author(s):  
Feng-Che Kuan ◽  
Wei-Hsun Yang ◽  
Hung-Yi Lai ◽  
Chun-Chieh Huang ◽  
Cheng-Ta Yang ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lung Adenocarcinoma ◽  
Egfr Mutations ◽  
Outcome Analysis ◽  
P Value ◽  
Research Database ◽  
Poor Prognostic Factor ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Egfr Mutated

e13588 Background: BM represent a common problem in EGFR-mutated lung adenocarcinoma. The updated Lung-molGPA elucidates the survival in patients with non-small-cell lung cancer and BM by incorporating the effect of EGFR gene alterations. However, the nature history and differences of prognostic implication between common and uncommon EGFR mutations remain unsolved. Methods: By retrospective analysis of Chang-Gung Research Database (CGRD), patients with EGFR-mutated lung adenocarcinoma and BM were included into analysis of PFS and OS. EGFR mutations were categorized into exon 19 deletions (Del19), exon 21 Leu858Arg substitution (L858R) and uncommon mutations. Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models was performed to estimate adjusted hazard ratios (HR) and 95% confidence interval (CI). The p-value was set to be statistically significant at 0.05 or less. Results: From April 1, 2014 to June 30, 2015, 269 out of 818 patients with EGFR-mutated lung adenocarcinoma and BM were included, of which 115 patients with Del19, 131 patients with L858R, and 23 patients with uncommon EGFR mutations. The baseline characteristics were balanced in age, gender, KPS, ECM, number of BM, and timing of BM. In comparison with those with L858R, uncommon mutations is a poor prognostic factor for PFS (HR 2.24, 95% CI: 1.34-3.75, p = 0.002). The median PFS of Del 19, L858R, and uncommon EGFR mutations were 10.4, 10.0, and 3.2 months, respectively (log-rank p = 0.03). Besides, the median OS of Del 19, L858R, and uncommon EGFR mutations were 18.1, 17.4, and 12.5 months, respectively (log-rank p = 0.05). In comparison with those treated with gefitinib, afatinib treatment is a good prognostic factor for PFS and OS (PFS, HR 0.57, 95% CI: 0.35-0.94, p = 0.03; OS, HR 0.48, 95% CI: 0.26-0.91, p = 0.03). The median PFS of those treated with sequential WBRT, concurrent WBRT and TKI alone were 11.0, 8.5, and 10.3, respectively (log-rank p = 0.63). In addition, the median OS of those treated with sequential WBRT, concurrent WBRT and TKI alone were 18.7, 15.2, and 18.2 months, respectively (log-rank p = 0.50). Conclusions: Among patients with EGFR-mutated adenocarcinoma, common and uncommon EGFR mutations have distinct natural history and prognostic implications in patients with BM.

Project Switch: Docetaxel as a potential synthetic control in metastatic non-small cell lung cancer (mNSCLC) trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9105-9105 ◽  
Author(s):  
Michael E. Menefee ◽  
Yutao Gong ◽  
Pallavi Shruti Mishra-Kalyani ◽  
Rajeshwari Sridhara ◽  
Bindu Kanapuru ◽  
...  
Keyword(s):  
Randomized Trials ◽  
Progression Free Survival ◽  
Experimental Therapy ◽  
Synthetic Control ◽  
Small Cell Lung ◽  
Free Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Real World Evidence ◽  
The Impact

9105 Background: Docetaxel is a common comparator arm to test novel therapies in post-platinum mNSCLC trials. The advent of Real World Evidence (RWE) has renewed interest in the use of synthetic control arms (control arms from previously conducted randomized trials) to improve accrual to trials and increase patient access of promising experimental agents. We reviewed legacy second-line (2L) mNSCLC trials to assess the impact of switching docetaxel control arms from one trial to another and compare to an experimental regimen. Methods: We identified 5 contemporary 2L trials that enrolled 2013 patients receiving an experimental therapy vs. docetaxel: 5 immunoncology head-to-head trials (one with 2 arms) and one anti-VEGF add-on trial. Kaplan-Meier curves of overall survival (OS) and progression-free survival (PFS) were produced for docetaxel controls. We calculated OS and PFS hazard ratios and 95% confidence intervals for each synthetic trial. A pooled doc arm was also compared with each experimental agent. Results: See Table. Conclusions: Both individual and pooled docetaxel switching of control arms approximated the original OS HR and 95% CI. Methods such as bootstrapped sampling and propensity score matching will be performed in an effort to more closely approximate the original trial characteristics. [Table: see text]

Outcomes of KRAS mutated, EGFR mutated, ALK mutated and wildtype patients in non-small cell lung cancer brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21028-e21028
Author(s):  
Yasmeen Rauf ◽  
Vineeth Tatineni ◽  
Patrick joseph Oshea ◽  
Xuefei Jia ◽  
David M. Peereboom ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Retrospective Study ◽  
Brain Metastases ◽  
Targeted Therapies ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Alk Positive ◽  
Egfr Mutated

e21028 Background: Non-small cell lung cancer (NSCLC) is the most common primary tumor leading to brain metastases. Multiple genetic markers have been profiled in NSCLC patients for potential targeted therapies. EGFR is mutated in up 50% of NSCLCs, while ALK is mutated in around 4-7%. KRAS is the most commonly overexpressed marker, seen in up to 85% of all lung cancers. In this retrospective study, we evaluated the overall survival (OS) and progression-free survival (PFS) between NSCLCBM patients with KRAS mutations, ALK mutations, EGFR mutations, and wildtype. Methods: NSCLCBM patients diagnosed between 2010 and 2019 were analyzed. We collected information regarding molecular marker status, systemic therapies, and date of progression. We defined OS as the date of diagnosis of brain metastases to the date of last follow-up or death. OS and PFS were estimated by the Cox proportional model. Results: We found a total of 2989 NCSLCBM patients, 184 were KRAS mutated, 68 had an ALK gene rearrangement, 184 were EGFR mutated, and 1469 were wildtype. The respective median age was 64.3 years, 64.5 years, 58.2 years, and 64.2 years. Females made up 61.8% of KRAS-positive, 51.8% of ALK-positive, 63% of EGFR-positive, and 46.4% of wildtype patients. The median OS (mOS) in patients who were KRAS-positive, ALK-positive, EGFR-positive, and wildtype were 43.3 months, 119.2 months, 57.9 months, and 33.1 months, respectively. The median PFS (mPFS) for the same cohort was 38.0 months, 112.4 months, 55.3 months, and 30.5 months, respectively. ALK-positive patients showed statistically significant mOS (p-value (p) < 0.001) and mPFS (p = 0.002) when compared to EGFR-positive, KRAS-positive, and wildtype patients. Conclusions: Molecular mutations serve as both prognostic predictors and alternative targeted therapies for NSCLCBM treatment. Our retrospective study showed improved mOS and mPFS in NSCLCBM patients with ALK rearrangements when compared to patients with EGFR mutations, KRAS mutations, and the wildtype. While these results looked at patient outcomes with specific tumor markers, further investigation needs to be done regarding outcomes of specific therapies in each cohort, as well as, intracranial lesion response.

scholarly journals Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlos Loucera ◽  
María Peña-Chilet ◽  
Marina Esteban-Medina ◽  
Dolores Muñoyerro-Muñiz ◽  
Román Villegas ◽  
...  
Keyword(s):  
Vitamin D ◽  
Retrospective Cohort ◽  
Patient Survival ◽  
Endocrine System ◽  
Vitamin D Metabolites ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Real World Evidence ◽  
Central Registry ◽  
Health Database

AbstractCOVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15–30 days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan–Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95% confidence interval, CI, of [0.50–0.91]) than for cholecalciferol (HR = 0.75, with 95% CI of [0.61–0.91]), when prescribed 15 days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30 days prior hospitalization is considered (calcifediol HR = 0.73, with 95% CI [0.57–0.95] and cholecalciferol HR = 0.88, with 95% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization.

Prevalence of EGFR mutations in non-small cell lung cancer (NSCLC) smoker patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21015-e21015 ◽  
Author(s):  
Yann Izarzugaza ◽  
Manuel Domine ◽  
Federico Rojo ◽  
Victoria Casado ◽  
Ana Leon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20 ◽  
Egfr Mutated ◽  
Exon 19

e21015 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better response to tyrosine kinase inhibitors compared to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies in caucasian population have reported a frequency of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in caucasian smoker patients with NSCLC. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletions, 9 (50%) exon 21 mutations (7 cases L858R and 2 cases L861Q) and 3 (16.6%) exon 20 insertions. In the EGFR-mutated patients, 13 (72.25%) were never-smoker and 5 (27.7%) were smoker (3 current-smoker and 2 former-smoker). The EGFR-mutated smoker population showed the following characteristics: 3 female, 2 male; 4 adenocarcinoma, one squamous cell carcinoma; 3 stage IV, 2 stage IA at diagnosis; 1 (20%) case EGFR deletion exon 19, 1 (20%) case insertion exon 20 and 3 patients (60%) mutation exon 21 (2, L858R and 1, L861Q). Conclusions: The EGFR mutation rate in NSCLC smoking patients in our referral area is superior (27.7%) than previously reported, reinforcing the importance of including EGFR mutation testing in NSCLC smoking population for the correct management of these patients.

Prevalence of EGFR mutations in the Peruvian population: Study in a large cohort of patients with NSCLC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13076-e13076 ◽  
Author(s):  
Luis Mas ◽  
Christian Piscocha ◽  
Jose Landa ◽  
Carlos Roe ◽  
Eduardo Roe ◽  
...  
Keyword(s):  
Latin American ◽  
Small Sample ◽  
Large Cohort ◽  
Egfr Mutations ◽  
Reference Laboratory ◽  
Mutational Status ◽  
Exon 20 ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Exon 19

e13076 Background: The evaluation of EGFR mutational status of the EGFR in non-small cell lung cancer (NSCLC) is crucial to select the adequate targeted therapy and to know the outcome of patients. Previous studies in relative small sample sizes have described a higher prevalence of EGFR mutations in Peruvian population than other Latin American countries. Our aim in this study was to determine the prevalence of activating and resistance mutations of EGFR in a large cohort of Peruvian patients. Methods: We profiled metastatic tumor samples from 847 NSCLC patients for known EGFR mutations associated to sensitivity or resistance EGFR inhibitors, including exon 18 (G719X), exon 19 (deletions), exon 20 (T790M, S768I and insertions) and exon 21 (L858R). All samples were centrally tested in reference laboratory (Roe laboratory, Lima-Peru). Results: A total of 847 samples were profiled for EGFR mutational status. EGFR mutations were present in 32.9% of cases (n = 279). In regard to distribution of mutations in cases EGFR mutated, G719X (in exon 18) was present in 2.5% (n = 7); deletions in exon 19 had a frequency of 58.4% (n = 163). Mutations in exon 20 were present in 9.7% (n = 27). In patients with exon 20 mutated, 14 cases had insertions, 9 cases had the mutation T790M and 4 cases had the mutation S768I. Mutation L858R (exon 21) was present in 34.1% (n = 95) of cases. Coexistence of two mutations were present in exon 18/exon 20 (n = 1), exon 19/exon 20 (n = 7) and exon 20/ exon 21 (n = 5). In tumors with EGFR mutated. The sensible profile for EGFR tyrosine kinase inhibitors (TKI´s) was present in 96.8% of cases (n = 138). Conclusions: We have a high prevalence of EGFR mutations compared than Caucasian or other Hispanic cohorts. It has relevance in the Peruvian public health because more efforts should be done to screen NSCLC patients for EGFR mutations.

Real-world evidence: Adjuvant chemotherapy in colorectal cancer with liver metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16008-e16008
Author(s):  
Feng-Che Kuan ◽  
Gengping Lin ◽  
Chih-Chien Chin ◽  
Wen Shih Huang ◽  
Chung-Wei Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Liver Metastases ◽  
Research Database ◽  
Biologic Drugs ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Real World Evidence

e16008 Background: Systematic chemotherapy with biologics improves survival in metastatic colorectal cancer (mCRC). Oxaliplatin-based adjuvant chemotherapy is suggested in stage III and high-risk stage II CRC. However, whether adjuvant oxaliplatin-based chemotherapy remains standard treatment in CRC with liver metastases after hepatectomy is not elucidated. Methods: Medical records were searched in Chang-Gung Research Database from 2004 to 2017. Patients with CRC and liver metastases who received systematic therapies and salvage hepatectomy were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Total 454 patients received upfront hepatectomy (cohort 1) and 232 patients received neoadjuvant chemotherapy +/- biologics and salvage hepatectomy (cohort 2) were included in this study. In cohort 1 or cohort 2, the baseline characteristics of those received either postoperative oxaliplatin-containing regimen or other systematic regimens were not statistically different in gender, age, primary site, and biologic drugs. In cohort 1, overall survival (OS) in those received postoperative oxaliplatin-containing chemotherapy was significantly better than that of those received non-oxaliplatin-containing chemotherapy (median OS: 6.6 vs. 4.5 years, Log-rank p = 0.032; 5-year survival rate: 57.5 vs. 47.0%). In cohort 2, OS in those received postoperative oxaliplatin-containing chemotherapy was similar with that of those received irinotecan or biologics-containing chemotherapy (median OS: 3.1 vs. 3.5 vs. 3.8 years, Log-rank p = 0.472; 5-year survival rate: 30.9 vs. 33.3 vs. 37.0%). Conclusions: Oxaliplatin-containing chemotherapy provides better OS and remains standard adjuvant treatment in CRC with liver metastases after upfront hepatectomy. However, adjuvant chemotherapy in those received neoadjuvant chemotherapy +/- biologics and salvage hepatectomy should be individualized. Further prospective studies are warranted to validate these findings.

scholarly journals Heterogeneous Responses to Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) in Patients with Uncommon EGFR Mutations: New Insights and Future Perspectives in this Complex Clinical Scenario

2019 ◽  
Vol 20 (6) ◽  
pp. 1431 ◽  
Author(s):  
Alessandro Russo ◽  
Tindara Franchina ◽  
Giuseppina Ricciardi ◽  
Alessandra Battaglia ◽  
Maria Picciotto ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Epidermal Growth ◽  
Egfr Mutated ◽  
Egfr Tkis ◽  
Exon 19

Uncommon Epidermal Growth Factor Receptor (EGFR) mutations represent a distinct and highly heterogeneous subgroup of Non-Small Cell Lung Cancers (NSCLCs), that accounts for approximately 10% of all EGFR-mutated patients. The incidence of uncommon EGFR mutations is growing, due to the wider adoption of next-generation sequencing (NGS) for diagnostic purposes, which enables the identification of rare variants, usually missed with available commercial kits that only detect a limited number of EGFR mutations. However, the sensitivity of uncommon mutations to first- and second-generation EGFR Tyrosine Kinase Inhibitors (TKIs) is widely heterogeneous and less well known, compared with classic mutations (i.e., exon 19 deletions and exon 21 L858R point mutation), since most of the pivotal studies with EGFR TKIs in the first line, with few exceptions, excluded patients with rare and/or complex variants. Recently, the third generation EGFR TKI osimertinib further revolutionized the therapeutic algorithm of EGFR-mutated NSCLC, but its role in patients harboring EGFR mutations besides exon 19 deletions and/or L858R is largely unknown. Therefore, a better knowledge of the sensitivity of uncommon mutations to currently available EGFR TKIs is critical to guiding treatment decisions in clinical practice. The aim of this paper is to provide a comprehensive overview of the treatment of NSCLC patients harboring uncommon EGFR mutations with currently approved therapies and to discuss the emerging therapeutic opportunities in this peculiar subgroup of patients, including chemo-immunotherapy combinations, next-generation EGFR TKIs, and novel targeted agents.

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