scholarly journals Radiotherapy With Continued EGFR-TKIs for Oligoprogressive Disease in Non–Small Cell Lung Cancer: A Real-World Study

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 214s-214s
Author(s):  
C. Hu ◽  
S. Wu ◽  
F. Wu
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Smoking Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tkis

Introduction: Almost all epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) will develop tyrosine kinase inhibitors (TKIs) resistance. The treatment of oligoprogression is debatable after TKIs resistance. We conducted a real-world retrospective study to evaluate the efficacy of radiotherapy and continuation of TKIs in advanced NSCLC patients with oligoprogressive disease after EGFR-TKIs. Methods: From January 2011 to January 2018, we retrospectively analyzed EGFR-mutated NSCLC patients with oligoprogression in our institution. 33 patients were treated by radiotherapy and continuation of TKIs. We used Kaplan-Meier and Cox regression model to analyze the prognostic factors of progression-free survival (PFS) and overall survival (OS) from the time of oligoprogression. Variables we selected for analyses included gender, age, smoking status, performance status (PS) score, stage at initial diagnosis, initial resectable, radiotherapy dose, EGFR mutation type, number of metastasis, sites of radiation, T790M status, time of oligometastasis to radiotherapy. Results: 33 patients develop resistance to EGFR TKIs at a median time of 11.0 months. The mPFS and mOS were 6.5 and 21.0 months, respectively. T790M mutation was tested in 8 patients. The mPFS was 11.3 months in T790M mutation positive patients and 6.0 months in negative patients. The mPFS of patients with brain, lung, and bone metastases were 5.7, 6.0, and 13.0 months, respectively. The mPFS in patients who started radiotherapy within or beyond 1 month after oligometastasis was 11.0 months and 5.3 months. The mPFS of patients with postoperative recurrence and initial unresectable were 13.0 and 6.0 months, respectively. Patients with 1 or more than 1 metastatic site showed a mPFS of 11.0 and 4.4 months, respectively. Those who had EGRF exon 21 mutation achieved a mPFS of 11.3 months, whereas those with EGRF exon 19 mutation did worse with a mPFS of 6.5 months. Cox regression model showed no variables significantly correlated with PFS difference. Univariate analysis identified age and smoking status were significantly associated with OS. The results of multivariate analysis indicated that there was no OS-related prognostic factors. Conclusion: Radiotherapy with continued TKIs is an efficacious treatment option in our patients. Age and smoking status were prognostic factors for OS. Our research showed that there was a better survival in patients with T790M mutation, EGRF exon 21 mutation, radiotherapy within 1 month after oligometastasis and bone metastases. However, this was not statistically significant. Prospective studies are needed to validate these clinical results.

Radiotherapy with continued EGFR-TKIs for oligoprogressive disease in non-small cell lung cancer: A real-world study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20640-e20640
Author(s):  
Fang Wu ◽  
Sixuan Wu ◽  
Chunhong Hu
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Advanced Nsclc ◽  
Cox Regression ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tkis

e20640 Background: Almost all epidermal growth factor recept (EGFR)-mutated non-small-cell lung cancer (NSCLC) will develop tyrosine kinase inhibitors (TKIs) resistance. The treatment of oligoprogression is debatable after TKIs resistance. We conducted a real-world retrospective study to evaluate the efficacy of radiotherapy and continuation of TKIs in advanced NSCLC patients with oligoprogressive disease after EGFR-TKIs. Methods: From January 2011 to January 2019, we retrospectively analyzed EGFR-mutated NSCLC patients with oligoprogression in our institution. 33 patients were treated by radiotherapy and continuation of TKIs after oligoprogression. We used Kaplan-Meier and Cox regression model to analyse the prognostic factors of median progression-free survival (PFS) and median overall survival (OS) from the time of oligoprogression. Variables we selected for analyses included gender, age, smoking status, performance status (PS) score, stage at initial diagnosis, initial resectable, radiotherapy dose, EGFR mutation type, number of metastasis, sites of radiation, T790M status and the time of oligometastasis to radiotherapy. Results: 33 patients develop resistance to EGFR-TKIs at a median time of 11.0 months. The mPFS and mOS were 6.5 (95%CI, 1.4-11.6) and 21.8 (95%CI, 14.8-28.8) months, respectively. T790M mutation was tested in nine patients, four of which were mutation negative and five were positive. The mPFS was 15.5 (95%CI, 7.4-23.6) months in T790M mutation positive patients and 6.0 (95%CI, 0-14.0) months in negative patients. The mPFS in patients who started radiotherapy within or beyond 1 month after oligometastasis was 10.8 months (95% CI, 4.9-16.7 months) and 5.3 months (95% CI, 2.4-8.2 months). Cox regression model showed no variables significantly correlated with PFS difference. Univariate analysis identified female patients have longer OS (P = 0.038). The results of Multivariate analysis indicated that there was no OS-related prognostic factors. Conclusions: Radiotherapy with continued TKIs is an efficacious treatment option in advanced NSCLC patients with oligoprogressive disease after EGFR-TKIs. T790M mutation is a common mutation in NSCLC patients with oligoprogression. Gender was prognostic factors for OS. Moreover, there was a better prognosis in patients with T790M mutation positive or radiotherapy within 1 month after oligometastasis. However, this was not statistically significant. Larger sample size studies are needed to validate these clinical results.

scholarly journals Clinical Characteristics of Osimertinib Responder in Non-Small Cell Lung Cancer Patients with EGFR-T790M Mutation

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 365 ◽  
Author(s):  
Akihiro Yoshimura ◽  
Tadaaki Yamada ◽  
Naoko Okura ◽  
Takayuki Takeda ◽  
Kazuki Hirose ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr T790m ◽  
Egfr Tkis

Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively). Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation.

Impact of coexisting gene mutations in EGFR-mutated non–small cell lung cancer before treatment on EGFR T790M mutation status after EGFR-TKIs

Lung Cancer ◽  
2020 ◽  
Vol 139 ◽  
pp. 28-34
Author(s):  
Masayuki Takeda ◽  
Kazuko Sakai ◽  
Hidetoshi Hayashi ◽  
Kaoru Tanaka ◽  
Koji Haratani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Gene Mutations ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Mutation Status ◽  
Egfr Mutated ◽  
Egfr T790m ◽  
Egfr Tkis

scholarly journals Feasibility and effectiveness of afatinib for poor performance status patients with EGFR-mutation-positive non-small-cell lung cancer: a retrospective cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chiao-En Wu ◽  
Ching-Fu Chang ◽  
Chen-Yang Huang ◽  
Cheng-Ta Yang ◽  
Chih-Hsi Scott Kuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Disease Control ◽  
Performance Status ◽  
Poor Performance ◽  
Small Cell ◽  
Poor Performance Status ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Afatinib is one of the standard treatments for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). However, data on the use of afatinib in patients with poor performance status (PS ≥ 2) are limited. This study aimed to retrospectively review the clinical outcomes and safety of afatinib treatment in EGFR-mutation-positive (EGFRm+) NSCLC patients with PS ≥ 2. Methods The data for 62 patients who were treated at Linkou Chang Gung Memorial Hospital from January 2010 to August 2019 were retrospectively reviewed. Patients’ clinicopathological features were obtained, and univariate and multivariate analyses were performed to identify possible prognostic factors. Data on adverse events were collected to evaluate general tolerance for afatinib therapy. Results Until February 2020, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 58.1% (36/62), 69.4% (43/62), 8.8 months, and 12.9 months, respectively. The absence of liver metastasis (PFS: p = 0.044; OS: p = 0.061) and good disease control (p < 0.001 for PFS and OS) were independent favorable prognostic factors for PFS and OS. Bone metastasis (p = 0.036) and dose modification (reduction/interruption, p = 0.021) were predictors of disease control. Conclusion Afatinib demonstrated acceptable efficacy and safety in the current cohort. This study provided evidence to support the use of afatinib as a first-line treatment in EGFRm+ NSCLC patients with poor PS.

Treatment in EGFR-mutated Non-small Cell Lung Cancer: How to Block the Receptor and overcome Resistance Mechanisms

2017 ◽  
Vol 103 (4) ◽  
pp. 325-337 ◽  
Author(s):  
Claudia Proto ◽  
Giuseppe Lo Russo ◽  
Giulia Corrao ◽  
Monica Ganzinelli ◽  
Francesco Facchinetti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Small Cell ◽  
Third Generation ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Exon 20 ◽  
Egfr Mutated ◽  
Egfr Tkis

In non-small cell lung cancer (NSCLC), the identification of epidermal growth factor receptor (EGFR) mutations and the parallel development of EGFR tyrosine kinase inhibitors (TKIs) have radically changed the therapeutic management strategies. Currently, erlotinib, gefitinib, and afatinib are all approved as standard first-line treatment in EGFR-mutated NSCLC. However, despite the proven efficacy, some EGFR-mutated NSCLCs do not respond to EGFR TKIs, while some patients, after a favorable and prolonged response to EGFR TKIs, inevitably progress within about 10-14 months. Epidermal growth factor receptor-dependent mechanisms, activation of alternative pathways, or phenotypic transformation can cause the resistance to EGFR TKIs. The exon 20 p.Thr790Met point mutation (T790M) is responsible for about 60% of cases of resistance when progression occurs. A third-generation TKI, osimertinib, improved outcome in patients harboring T790M after first- and second-generation TKI treatment. However, resistance develops even after treatment with third-generation drugs. To date, the Cys797Ser (C797S) mutation in exon 20 of EGFR is the most well-known resistance mutation after osimertinib. Fourth-generation TKIs are already under development. Nevertheless, additional information is needed to better understand and effectively overcome resistance. The aim of this review is to report recent advances and future perspectives in the treatment of EGFR-mutated NSCLC, highlighting the resistance mechanisms that underlie disease progression.

ERK Inhibitor ASN007 Effectively Overcomes Acquired Resistance to EGFR Inhibitor in Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Bo Mi Ku ◽  
Jae Yeong Heo ◽  
Jinchul Kim ◽  
Jong-Mu Sun ◽  
Se-Hoon Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Erk Signaling ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr Tkis

Abstract The emergence of acquired resistance limits the long-term efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Thus, development of effective strategies to overcome resistance to EGFR-TKI is urgently needed. Multiple mechanisms to reactivate ERK signaling have been successfully demonstrated in acquired resistance models. We found that in EGFR mutant non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs was accompanied by increased activation of ERK. Increased ERK activation was also found in in vitro models of acquired EGFR-TKI resistance. ASN007 is a potent selective ERK1/2 inhibitor with promising antitumor activity in cancers with BRAF and RAS mutations. ASN007 treatment impeded tumor cell growth and the cell cycle in EGFR-TKI-resistant cells. In addition, combination treatment with ASN007 and EGFR-TKIs synergistically decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR-TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR-TKIs by overcoming acquired resistance.

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