Skin toxicity associated with outcome to erlotinib in non-small cell lung cancer (NSCLC) patients (p) with EGFR mutations in the EURTAC study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7542-7542
Author(s):  
Cristina Buges ◽  
Alex Martinez Marti ◽  
Rafael Rosell ◽  
Alain Vergnenegre ◽  
Filippo De Marinis ◽  
...  
Keyword(s):  
Skin Rash ◽  
Smoking Status ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Egfr Mutations ◽  
Free Survival ◽  
Nsclc Patients ◽  
First Time ◽  
To Receive ◽  
Exon 19

7542 Background: Rash is reported in 75% of p treated with erlotinib and has been associated with improved overall and progression-free survival (PFS) in unselected p although not specifically in p with EGFR mutations. Methods: The EURTAC trial (clinicaltrials.gov NCT00446225) randomized 174 p with EGFR exon 19 deletions or L858R mutations to receive erlotinib or chemotherapy. Overall PFS was 9.7 months (m) vs 5.2 m, respectively (P<0.0001). Rash was defined according to NCI CTC v3.0 and dichotomized by grades 0-1 vs 2+. Grade 2 is macular or popular eruption or erythema with pruritus or other associated symptoms, localized desquamation or other lesions covering <50% of body surface area. We examined outcome in the erlotinib arm according to rash grade. Results: 16 p in the erlotinib arm had no rash (grade 0), 30 had grade 1, and 40 had grade 2+. 80% of cases of rash grade 2+ occurred in p with exon 19 deletions, while only 20% were in p with L858R mutations (P=0.039). There were no differences in rash grade according to sex, age or smoking status. PFS was 11.2 m in p with rash grade 2+ and 8.4 m in p with grade 0-1 (HR, 0.52; P=0.018). There was no correlation between rash grade 0-1 vs 2+ and response or overall survival (OS). Interestingly, when p were divided into those with no rash (16 p) and those with grade 2+ (40 p), PFS was 11.2 m for p with grade 2+ vs 2.7 m for p with no rash (P=0.031), and OS was 24.9 m for p with grade 2+ vs 16.1 m for p with no rash (P=0.033). Conclusions: Although the biological reasons for the association of skin rash with better outcome to erlotinib have not been elucidated, this sub-analysis of the EURTAC trial has enabled us to confirm for the first time that skin rash – especially grade 2+ - can predict better outcome to erlotinib in p with EGFR mutations. In addition, the correlation between rash and type of EGFR mutation warrants further investigation.

Differential progression-free survival (PFS) to erlotinib according to EGFR exon 19 deletion type in non-small cell lung cancer (NSCLC) patients (p) in the EURTAC study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7540-7540
Author(s):  
Enric Carcereny Costa ◽  
Miquel Taron ◽  
Cristina Queralt ◽  
Itziar de Aguirre ◽  
Laia Capdevila ◽  
...  
Keyword(s):  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
In Vitro Sensitivity ◽  
Duration Of Response ◽  
Exon 19 Deletion ◽  
Nsclc Patients ◽  
To Receive ◽  
Exon 19

7540 Background: Different exon 19 deletion types have shown different in vitro sensitivity to erlotinib, with the lower IC50 for deletion E746_A750 (ELREA) (Yuza et al. Cancer Biol Ther 2007). This information prompted us to examine outcome according to type of exon 19 deletion in the EURTAC study. Methods: The EURTAC trial (clinicaltrials.gov NCT00446225) randomized 174 p with EGFR exon 19 deletions or L858R mutations to receive erlotinib or chemotherapy. Progression-free survival (PFS) was 9.7 months (m) vs 5.2 m, respectively (P<0.0001). Exon 19 deletions were divided into two groups: ELREA vs non-ELREA deletions. Results: Exon 19 deletions were present in 57 p in the erlotinib arm and in 58 p in the chemotherapy arm. ELREA deletions were found in 41 p (71.9%) in the erlotinib arm and in 38 p (65.5%) in the chemotherapy arm. Non-ELREA deletions were found in 16 p in the erlotinib arm and in 20 p in the chemotherapy arm. There were no differences in p characteristics between treatment arms according to type of deletion. PFS for p with ELREA deletions was 9.4 m in the erlotinib arm and 4.6 in the chemotherapy arm (HR, 0.36; P=0.0004). PFS for p with non-ELREA deletions was not reached in p in the erlotinib arm and was 5.3 m for p in the chemotherapy arm (HR, 0.17; P=0.001). The multivariate analysis identified erlotinib arm (P<0.001) and non-ELREA deletions (P=0.001) as independent markers of longer PFS. Overall survival (OS) for p with ELREA deletions was 17 m in the erlotinib arm and 18.4 in the chemotherapy arm (P=0.575). OS for p with non-ELREA deletions was not reached in the erlotinib arm and 19.5 m in the chemotherapy arm (P=0.216). Response rate (RR) for p with ELREA deletions was 53.6% in the erlotinib arm vs 15.7% in the chemotherapy arm (P=0.004). RR for p with non-ELREA deletions was 68.7% in the erlotinib arm vs 10% in the chemotherapy arm (P=0.001). Conclusions: To date, no biological reason has been identified that can explain the greater sensitivity to erlotinib in p with non-ELREA exon 19 deletions. Our findings indicate the need to define the type of deletion prior to treatment since this information can be helpful in predicting the duration of response.

scholarly journals Efficacy of First-Third generation EGFR inhibitor combined with chemotherapy as first-line treatment for advanced lung adenocarcinoma in a real-world setting

2021 ◽  
Author(s):  
Ming-Wei Chen Ming-Wei Chen ◽  
An-Tai He . ◽  
Yi Pei .
Keyword(s):  
Lung Adenocarcinoma ◽  
Survival Time ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Combination Group ◽  
First Line ◽  
Free Survival ◽  
Mean Survival Time ◽  
First Line Therapy ◽  
To Receive

Abstract BackgroundTo explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head-to-head study was performed to compare chemotherapy and gefitinib-erlotinip, osimertinib treatment in combination or with either agent alone as first-line therapy, in terms of efficacy and safety.MethodsA total of 200 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib-erlotinip combined with pemetrexed and carboplatin group, gefitinib-erlotinip osimertinib combined with pemetrexed and carboplatin group, pemetrexed plus carboplatin alone group, or gefitinib-erlotinip alone group, osimertinib alone group.ResultsThe progression-free survival (PFS) of patients in the gefitinib-erlotinip combination group Mean Survival Time PFS 22.00 month,95%CI[16.29,27.70] and osimertinib gefitinib-erlotinip combination group Mean Survival Time PFS 40.00 month,95%CI[28.12,51.87]was longer than that of patients in the chemotherapy alone group PFS10,81 months, 95% CI,[ 8.99–12.64],gefitinib-erlotinip alone group PFS14.00 month.95%CI[11.98-20.01], osimertinib alone group PFS 26.66 month 95%CI[24.77-29.22].The gefitinib-erlotinip osimertinib combinational resulted in longer overall survival (OS) than chemotherapy alone (HR = 0.46, p = 0.016) or gefitinib-erlotinip alone (HR = 0.36, p = 0.01). osimertinib alone (HR = 0.26, p = 0.01).ConclusionsOur finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib-erlotinip and pemetrexed plus carboplatin combined with gefitinib-erlotinip osimertinib group could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.

A meta-analysis of comparing EGFR-TKI with chemotherapy as the second-line treatment of NSCLC patients with wild-type EGFR.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19166-e19166 ◽  
Author(s):  
Guanghui Gao ◽  
Shengxiang Ren ◽  
Aiwu Li ◽  
Yayi He ◽  
Xiaoxia Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Overall Response ◽  
Nsclc Patients ◽  
Egfr Tki

e19166 Background: The efficacy of comparing the EGFR-TKI with standard chemotherapy in the second-line treatment of advanced NSCLC with wide-type EGFR were still controversial. To derive a more precise estimation of the two regimens, a meta-analysis was performed. Methods: Medical databases and conference proceedings were searched for randomized controlled trials which compared EGFR-TKI (gefitinib or erlotinib) with standard second-line chemotherapy (docetaxel or pemetrexed) in patients with NSCLC. Endpoints were overall survival, progression-free survival and overall response. Results: Three eligible trials (INTEREST, TITAN and TAILOR) were identified. Lacking for data of overall survival of TAILOR trial, So we only make a preliminary meta-analysis for overall survival. The intention to treatment (ITT) analysis demonstrated that the patients receiving EGFR-TKI had a significantly shorter progression-free survival (PFS) than patients treated with chemotherapy (hazard ratio (HR) = 1.31; 95% confidence intervals (CI) = 1.10-1.56; P = 0.002). The overall survival (OS) and overall response rate (ORR) were coparable between this two groups (HR = 0.96; 95%CI = 0.77-1.19; P = 0.69; relative risk (RR) = 0.37; 95%CI = 0.09-1.54; P = 0.17). Conclusions: Although chemotherapy had a clear superiority in PFS as second-line treatment for patients without EGFR mutations compared with EGFR-TKI, OS and ORR were equal in this two regimens. The toxicity profiles might play an important role in the decision to choose EGFR-TKI or chemotherapy. These findings still need to be verified in larger confirmatory studies in future.

scholarly journals Effectiveness of Afatinib and Gefitinib in Non-Small Cell Lung Cancer (NSCLC) Epidermal Growth Factor Receptor (EGFR) Mutations in Indonesia: Observational Studies with Retrospectives

2019 ◽  
Vol 10 (4) ◽  
pp. 3516-3522
Author(s):  
Seftika Sari ◽  
Tri Murti Andayani ◽  
Dwi Endarti ◽  
Kartika Widayati
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Medical Records ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Effectiveness data can describe the results or performance of an intervention (treatment) in daily clinical practice and also provide recommendations to policymakers regarding the need or not of health technology to be implemented into the health care system. Research related to the effectiveness of afatinib and gefitinib is still minimal, especially in Indonesia. This study aims to provide an overview of the effectiveness of afatinib and gefitinib in daily clinical practice (the real world) as first-line therapy. This research is an observational study with a retrospective approach that observes the medical records of NSCLC patients who have EGFR mutations in Dr. Sardjito General Hospital Yogyakarta and Dr. Kariadi General Hospital Semarang, Java Island, Indonesia in the period January 2016 - March 2019. The effectiveness seen is the Progress Free Survival and Overall Survival based on the patient's medical records and analyzed using the Kaplan Meier test to see survival. There were 113 patients identified, 27 patients using afatinib and 86 patients using gefitinib. Afatinib had significantly superior progression-free survival (448 days or 14.7 months; 95% CI = 12-17.4 months; p = 0.002) compared to gefitinib (344 days or 11.3 months; 95% CI = 8, 4-14.3 months), however, overall survival of afatinib is no better than gefitinib (472 days or 15.5 months; 95% CI = 13.8-17.2 months vs 653 days or 21.4 months; 95% CI = 18-24.8 months) with a value of p = 0.302. Afatinib has superior progression-free survival compared to gefitinib, but not overall survival as first-line therapy in NSCLC patients with EGFR mutations.

Efficacy of gefitinib in patients with advanced non-small cell carcinoma of the lung harboring common, uncommon and complex EGFR mutations

2021 ◽  
Vol 08 ◽  
Author(s):  
Wang Chun Kwok ◽  
Ka Yan Chiang ◽  
James Chung Man Ho ◽  
Terence Chi Chun Tam ◽  
Mary Sau Man Ip ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Small Cell ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
First Line Treatment ◽  
Exon 19

Background: As the commonest EGFR-TKI being used in Hong Kong, gefitinib has shown to be efficacious and safe as first line treatment for L858R mutation and exon 19 deletion with less gastrointestinal and cutaneous adverse events than erlotinib and afatinib. However, the evidence for therapeutic efficacy for uncommon and complex EGFR mutations is lacking. Whether gefitinib is efficacious for uncommon and complex EGFR mutations worth studying. Objectives: To assess the therapeutic efficacy of gefitinib, as measured by progression-free survival and overall survival, among advanced stage lung cancer patients with common, uncommon and complex EGFR mutations. Methods: This is a retrospective cohort study that included 241 Chinese patients with advanced non-small cell carcinoma of lung harboring EGFR mutations and received gefitinib 250 mg daily as first-line treatment. The progression-free survival [PFS] and overall survival [OS] for patients with different EGFR mutations, namely exon 19 deletion, L858R mutation in exon 21, uncommon EGFR mutations and complex EGFR mutations were analyzed. Results: Among the 241 patients, 118 [49%] had exon 19 deletion, 104 [43%] had L858R mutation in exon 21, 6 [2.5%] had uncommon EGFR mutations, 13 [5.4%] had complex EGFR mutations. The mean age was 69. 72% of the patients were female and with 81% being non-smoker. For patients with complex EGFR mutations, regardless of the presence of exon 19 deletion and L858R mutation as the component, have better PFS and OS than patients with single common EGFR mutations [Exon 19 deletion or L858R mutation]. Patients with uncommon EGFR mutations have inferior PFS and OS than those with common EGFR mutations. Conclusion: Gefitinib is a possible option for patients with complex EGFR mutations while it may not be the preferred treatment option in patients with single uncommon EGFR mutations.

Response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with de novo epidermal growth factor receptor (EGFR) T790M and S768I resistance mutations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Deirdre Kelly ◽  
Lisa Mary Prior ◽  
Jack Patrick Gleeson ◽  
Lynda M. McSorley ◽  
Rachel Kearns ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stable Disease ◽  
De Novo ◽  
Objective Response ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Resistance Mutations ◽  
Free Survival ◽  
Nsclc Patients ◽  
Egfr Tkis

e20557 Background: Patients with synchronous de novo EGFR sensitising and resistance mutations are rare. Little is known about the response of these patients to EGFR TKIs, especially in a Caucasian population. Methods: We identified NSCLC patients found to have EGFR mutations using PCR-based fragment length analysis, mass spectrometry-based genotyping (Sequenom), and Sanger sequencing using a large multi-institutional database. Baseline clinical characteristics, response rate, progression free survival (PFS) and overall survival (OS) were calculated. Results: From 2008-2015, we observed de novo synchronous EGFR sensitising and resistance mutations in 12 patients representing an overall incidence of 3.6% of EGFR mutants and 0.4% of all NSCLC patients tested. Seven patients were treated using EGFR TKI therapy with erlotinib. In all cases, T790M (n = 4,50%) or S768I (n = 4, 50%) occurred concurrently with another sensitising EGFR mutation, either L858R (n = 4, 34%) or exon 19 deletion (n = 8, 66%). Objective responses were seen in two patients (29%). Three further patients had stable disease lasting 6, 23 and 54 months respectively. The median progression-free survival was 24 months and the median overall survival was 34 months. All patients with baseline EGFR S768I mutations (n = 3) had an objective response or stable disease on erlotinib while two of four patients with T790M demonstrated de novo resistance. Conclusions: This is the largest Irish review of synchronous de novo EGFR mutations. The incidence of co-occurring EGFR mutations was 0.4% and erlotinib demonstrated activity in this cohort of patients. Ongoing trials will determine whether next-generation EGFR TKIs such as osimertinib are preferable as first-line therapy in these patients.

Biological and clinical prognostic factors in patients with advanced non-small-cell cancer (NSCLC) treated by erlotinib: Preliminary results of the ERMETIC cohort

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8079-8079
Author(s):  
J. Cadranel ◽  
M. Beau-Faller ◽  
A. Mauguen ◽  
S. Lizard ◽  
J. Madelaine ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Cox Model ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Kras Mutations ◽  
Free Survival ◽  
Nsclc Patients ◽  
First Time ◽  
Egfr Tkis

8079 Background: Although it has been suggested that results of EGFR-IHC, EGFR-FISH and EGFR and KRAS mutations are predictive of EGFR-TKIs efficacy, they are not used in clinical practice. ERMETIC is a French NCI granted prospective study aiming to facilitate implementation of these biomarkers in France. Methods: After a preliminary phase of validation in 16 French centers, these biomarkers were studied in available tumor specimens collected from all consecutive NSCLC patients (pts) treated by erlotinib, for the first time. Patients were followed-up until progression or death. Demographic, clinical, pathological characteristics and biomarkers were studied by Cox model as predictors of progression free survival (PFS) and overall survival (OS). Results: 493 of the 530 enrolled pts between 02/07 and 03/08 are included in this analysis, among whom at least 357 (72%) tumor specimens were collected. 88% were Caucasians, 32% females; median age was 62 (33–93); 15% were never smoker, 67% former and 15% active. 18% were PS0, 51% PS1 and 31% PS2–3. 92% pts were metastatic and 66% had adenocarcinoma (ADC). Erlotinib (150 mg in 98% of pts) was given as first-, second- and third-or-more-line in 10, 45, 42% of pts, respectively. 94% of pts had received previous platin-based chemotherapy. With a 11.5 months (mo.) median of follow-up, PFS was 2.4 mo. and OS 5.6 mo., with a 30% 1-year OS. Clinical factors independently associated with shorter OS were: PS1 and PS2–3 (HR=1.79 and 4.3, p<.0001); histology other than ADC and squamous cell (HR=1.44 and 1.03, p=.05); 2 sites of metastasis and more (HR=1.60 and 1.82, p<.0001) and former and active smoking (HR=1.49 and 2.12, p=.002). In multivariate analysis, line of treatment was not prognostic. Conclusions: The study confirmed in a large cohort of advanced NSCLC treated by erlotinib the independent value of several prognostic factors. Prognostic values of EGFR-IHC, EGFR-FISH and EGFR and KRAS mutations will be reported at the meeting. [Table: see text]

Response to erlotinib and prognosis for patients with de novo epidermal growth factor receptor (EGFR) T790M mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8018-8018 ◽  
Author(s):  
Gregory J. Riely ◽  
Helena Alexandra Yu ◽  
Maria E. Arcila ◽  
Matthew David Hellmann ◽  
Marc Ladanyi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
De Novo ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Free Survival ◽  
Exon 19 Deletion ◽  
Egfr Tki ◽  
Egfr T790m ◽  
Exon 19

8018 Background: A secondary mutation in exon 20 of EGFR, T790M, is the most common cause of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR mutant lung cancers. De novo EGFR T790M mutations in TKI-naïve patients are rare when assessed by standard genotyping methods. The response to EGFR TKIs in patients with de novo EGFR T790M mutations is unknown. Methods: Patients with EGFRmutations were identified through routine testing, using PCR-based fragment length analysis, mass spectrometry-based genotyping (Sequenom), and Sanger sequencing. Clinical characteristics, progression free survival (PFS) from start of EGFR TKI and overall survival (OS) were obtained from the medical record. Results: From 2008-2012, we observed EGFR T790M in 21 tumors from 20 patients who had not previously been treated with an EGFR TKI representing <2% of all tumors with identified EGFR mutations. Two patients are included in reports from the Lung Cancer Mutation Consortium. The median age at lung cancer diagnosis was 57 (range 35-90). 55% presented with stage IV disease. 60% were women. 65% were never-smokers. In all cases, T790M occurred concurrently with another EGFR mutation, L858R (76%, 16/21) or exon 19 deletion (24%, 5/21). Compared to a contemporary cohort of 593 patients with EGFR mutations, in these patients with de novo EGFR T790M, L858R was more frequent than exon 19 deletion (p=0.003). Thirteen patients received erlotinib monotherapy as treatment for metastatic disease. Their response rate (CR+PR) was 9% (1/11, 95% Confidence Interval: 0-40%). SD was observed in 36% (4/11). The median progression-free survival was 3 months and the median overall survival was 16 months. Conclusions: De novo EGFR T790M mutations are rare and occur most commonly with EGFR L858R. Overall survival for patients with de novo EGFR T790 mutations is shorter than what is seen in patients with EGFR exon 19 deletions or L858R, and appears more similar to EGFR wild-type patients. Response rate to EGFR TKI in these patients is low. EGFR TKI therapy for patients with de novo EGFR T790M appears to have limited objective benefit and should be considered only after standard cytotoxic chemotherapy.

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