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 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.

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 Chinese Herbal Medicine Combined With First-Generation EGFR-TKIs in Treatment of Advanced Non-Small Cell Lung Cancer With EGFR Sensitizing Mutation: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Lu ◽  
Chenbing Sun ◽  
Lijing Jiao ◽  
Yu Liu ◽  
Yabin Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
First Generation ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Chinese Herbal ◽  
Nsclc Patients ◽  
Egfr Tkis

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve prognosis of advanced NSCLC patients harboring EGFR sensitizing mutation. However, acquired resistance to EGFR-TKIs limits the good outcomes. Chinese herbal medicine (CHM) has been used for NSCLC patients receiving EGFR-TKIs for more than 10°years as an adjuvant treatment.Methods: Studies were searched from China BioMedical Literature, Chinese National Knowledge Infrastructure, Cqvip Database, Wanfang Database, MEDLINE (PubMed), EMBASE (Ovid), Google Scholar, and Cochrane Library from inception to March, 2021. Randomized controlled clinical trials (RCT) comparing EGFR-TKIs + CHM (TKIs + CHM) versus EGFR-TKIs with/without placebo (TKIs ± placebo) in participants with advanced NSCLC harboring EGFR sensitizing mutation were included in this study. Two authors screened all references, assessed the risk of bias and extracted data independently. Data were summarized using hazard ratio (HR) and risk ratios (RR), with 95% confidence intervals (CI) for binary outcomes. Meta-analysis was performed using random effects model. Overall quality of evidence was assessed using GRADE.Results: A total of 9 RCTs (1137 participants, 581 in the TKIs + CHM group and 556 in the TKIs ± placebo group) were included in this review. Only first-generation EGFR-TKIs were included. Most trials included used oral CHM preparations to tonify Qi and/or Yin. Treatment lasted from enrollment until disease progression (PD) or intolerable adverse events (AE). Combination of CHM with EGFR-TKIs improved median progression-free survival (mPFS) (HR,0.59; 95% CI, 0.52–0.68; P < 0.00001) and objective response rate (ORR) (RR, 1.23; 95% CI, 1.13–1.34; P < 0.00001) compared with used of EGFR-TKIs ± placebo. CHM reduced AE associated with EGFR-TKIs such as cutaneous toxicity (RR, 0.58; 95% CI, 0.46–0.73; P < 0.00001) and diarrhea (RR, 0.43; 95% CI, 0.30–0.60; P < 0.00001).Conclusion: Combination therapy of CHM and EGFR-TKIs significantly delays acquired resistance while improving ORR to EGFR-TKIs. Furthermore, CHM reduces AE induced by EGFR-TKIs. More international multi-centered, double-blinded, placebo-controlled, well-designed clinical trials are needed in future research.

Effectiveness of osimertinib plus chemotherapy and avastin for untreated EGFR-mutated advanced non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21178-e21178
Author(s):  
Fang Wang ◽  
Hui Liu ◽  
Zhen Zeng ◽  
Shasha Wang ◽  
Haifeng Qin
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Mutated

e21178 Background: Osimertinib is recommended as a novel first-line standard treatment for advanced Non-Small-Cell Lung Cancer (NSCLC) patients with EGFR mutation. However, there are also patients with concurrent mutation or/and metastases have limited benefits. According to the current remission rate, regression depth and PFS data, the main mechanism of the benefit of combined anti-angiogenesis or chemotherapy is to reduce tumor load and heterogeneous reserve to a greater extent, so as to extend the remission time, that is, to delay the occurrence of drug resistance to extend PFS. This prospective study aims to investigate the efficacy and safety of Osimertinib plus chemotherapy and Avastin for Untreated EGFR-Mutated advanced NSCLC. Methods: The study enrolled 22 patients diagnosed with untreated advanced NSCLC and tested with EGFR mutation, who received osimertinib ( 80mg QD) plus pemetrexed (500mg/m2), cisplatin (75mg/m2) and bevacizumab (7.5mg/kg) for 6 cycles, then maintained with osimertinib/pemetrexed/bevacizumab. The primary endpoint was progression free survival (PFS). The secondary endpoint was objective response rate (ORR). Treatment was continued until disease progression and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The toxicity was determined according to CTCAE 4.0. Results: From February, 2018 to July, 2020, 22 patients enrolled. All the patients were evaluated and showed partial response(PR) when make efficacy evaluation at the first time. The target lesions reduction were shown. The average reduction is 48%, ranged from 32% of Pt12 to 71% of Pt11. Up to January, 2021, all the patients are still under the treatment. Especially for Pt7 who has already benefited from the treatment protocol by 35months. The toxicities associated with this protocols were manageable. Only 1 patient was 3/4-grade Anemia, 1 patient was 3/4-grade Diarrhea and 3 patients was 3/4-grade Lymphopenia. Conclusions: Osimertinib in combination with chemotherapy and Bevacizumab. exhibits superior activity and generally manageable toxicities for the naive advanced NSCLC patients with EGFR mutant, especially for the patients with concurrent mutation or/and metastases. It may provide a new and effective therapy strategy for them, but large sample and additional clinical trials are also needed.

Management and Future Directions in Non-Small Cell Lung Cancer with Known Activating Mutations

2014 ◽  
pp. e353-e365 ◽  
Author(s):  
David E. Gerber ◽  
Leena Gandhi ◽  
Daniel B. Costa
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Egfr Mutations ◽  
Symptom Improvement ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Egfr Tkis

Lung cancer accounts for a quarter of all cancer deaths. Non-small cell lung cancer (NSCLC) is currently segregated by the presence of actionable driver oncogenes. This review will provide an overview of molecular subsets of lung cancer, including descriptions of the defining oncogenes ( EGFR, ALK, KRAS, ROS1, RET, BRAF, ERBB2, NTRK1, FGFR, among others) and how these predict for response to small molecule tyrosine kinase inhibitors (TKIs) that are either clinically available or in clinical trial development for advanced NSCLC. Particular focus will be placed on subsets with EGFR mutated and ALK rearranged NSCLC. Somatic TKI-sensitizing EGFR mutations (such as exon 19 deletions and L858R substitutions) are the most robust predictive biomarker for symptom improvement, radiographic response, and increment in progression-free survival (PFS) when EGFR TKIs (gefitinib, erlotinib, and afatinib) are used for patients with advanced NSCLC. However, the palliative benefits that EGFR TKIs afford are limited by multiple biologic mechanisms of tumor adaptation/resistance (such as the EGFR-T790M mutation and oncogene bypass tracks), and future efforts toward delaying, preventing, and treating resistance are underway. Similar to EGFR mutations, ALK rearrangements exemplify an oncogene-driven NSCLC that can be effectively palliated with a precision TKI therapy (the multitargeted ALK/MET/ROS1 TKI crizotinib). When resistance to first-line crizotinib therapy occurs, multiple second generation ALK TKIs have demonstrated impressive rates of disease control in clinical trials, and these may modify long-term outcomes for patients with ALK-positive NSCLC. The development of TKIs for other oncogene-driven NSCLCs may expand the portfolio of precision therapies for this recalcitrant cancer.

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.

scholarly journals Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Wang ◽  
Zhixuan Ren ◽  
Bentong Yu ◽  
Jian Tang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Cancer Genomics ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Introduction Immune checkpoint inhibitors (ICIs) have become a frontier in the field of clinical technology for advanced non-small cell lung cancer (NSCLC). Currently, the predictive biomarker of ICIs mainly including the expression of PD-L1, TMB, TIICs, MMR and MSI-H. However, there are no official biomarkers to guide the treatment of ICIs and to determine the prognosis. Therefore, it is essential to explore a systematic nomogram to predict the prognosis of ICIs treatment in NSCLC Methods In this work, we obtained gene expression and clinical data of NSCLC patients from the TCGA database. Immune-related genes (IRGs) were downloaded from the ImmPort database. The detailed clinical annotation and response data of 240 advanced NSCLC patients who received ICIs treatment were obtained from the cBioPortal for Cancer Genomics. Kaplan–Meier survival analysis was used to perform survival analyses, and selected clinical variables to develop a novel nomogram. The prognostic significance of FGFR4 was validated by another cohort in cBioPortal for Cancer Genomics. Results 3% of the NSCLC patients harbored FGFR4 mutations. The mutation of FGFR4 were confirmed to be associated with PD-L1, and TMB. Patients harbored FGFR4 mutations were found to have a better prolonged progression-free survival (PFS) to ICIs treatment (FGFR4: P = 0.0209). Here, we built and verified a novel nomogram to predict the prognosis of ICIs treatment for NSCLC patients. Conclusion Our results showed that FGFR4 could serve as novel biomarkers to predict the prognosis of ICIs treatment of advanced NSCLC. Our systematic prognostic nomogram showed a great potential to predict the prognosis of ICIs for advanced NSCLC patients.

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