scholarly journals Efficacy and acquired resistance of EGFR-TKI combined with chemotherapy as first-line treatment for Chinese patients with advanced non-small cell lung cancer in a real-world setting

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting. Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity. Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.67–23.33] vs. 11.70 months [95% CI, 10.81–12.59], p < 0.001). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.30–41.70) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

scholarly journals Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

scholarly journals Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation

2020 ◽  
Vol 16 (21) ◽  
pp. 1537-1547
Author(s):  
Fumio Imamura ◽  
Madoka Kimura ◽  
Yukihiro Yano ◽  
Masahide Mori ◽  
Hidekazu Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Clinical Trial Registration

Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation EGFR-tyrosine kinase inhibitors was almost similar between FLAURA and ARCHER 1050, salvage use of osimertinib is still a treatment option. Patients & methods: We retrospectively analyzed the clinical courses of EGFR mutation-positive NSCLC patients who were potential candidates for salvage osimertinib. Results: Among 524 patients enrolled from five hospitals, 302 patients underwent biopsy, with 52.6% detection rate of T790M. Osimertinib was administered in 93.6% of the T790M-positive patients. The overall response rate and median progression-free survival time of osimertinib were calculated with 147 patients, to be 55.6% and 17.2 months, respectively. Conclusion: Osimertinib is active for T790M-driven acquired resistance in EGFR-mutant NSCLC, but the detection of T790M was unsatisfactory. Clinical Trial Registration: UMIN000028989 (UMIN Clinical Trials Registry)

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.

EGFR gene mutation is not a significant prognostic factor in patients with EGFR mutated non-small cell lung cancer who receive best supportive care alone.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21736-e21736
Author(s):  
Takeshi Masuda ◽  
Yu Wakabayashi ◽  
Kiyofumi Shimoji ◽  
Kakuhiro Yamaguchi ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Supportive Care ◽  
Egfr Mutation ◽  
Best Supportive Care ◽  
Small Cell ◽  
Significant Prognostic Factor ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki

e21736 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), are less toxic than conventional chemotherapy drugs, and benefit patients with EGFR-mutated non-small cell lung (NSCLC) cancer. However, there are a few patients who are not able to receive EGFR-TKI due to poor performance status, older age, or sever comorbidities. Here, we aimed to determine the prognostic significance of EGFR mutation in NSCLC patients who received best supportive care (BSC) alone, and compare the anti-tumor outcomes of only EGFR-TKI-treated patients vs. BSC patients. Methods: We retrospectively reviewed the medical records of patients diagnosed with NSCLC at Higashihiroshima Medical Center during April 1991–January 2019 and Hiroshima University Hospital during April 2008–August 2018. Results: A total of 1163 patients diagnosed with unresectable NSCLC were included in this analysis. Of these 1163 patients, 234 patients received BSC alone.Among 196 patients who underwent EGFR mutation analysis, 38 and 158 did and did not harbor an EGFR mutation, respectively, and the mean survival times (MST) did not differ significantly between these groups (121 vs. 85 days, p = 0.789). Consistent with the survival analysis, the multivariate Cox regression analyses showed EGFR mutation was not an independent prognostic factor. After propensity score matching, a comparison of only EGFR-TKI-treated (n = 35) and BSC patients (n = 35) with EGFR mutation revealed that the former had a significantly longer MST than the latter (372 vs. 121, p < 0.001). Conclusions: EGFR mutation itself was not a significant prognostic factor in untreated NSCLC patients. The patients who received EGFR-TKI had a significantly longer MST than their untreated counterparts. Our results may help to explain the benefit of EGFR-TKI, particularly for patients who would be directed towards treatment with BSC.

Final analysis of a phase II, open label, randomized study of osimertinib versus osimertinib plus carboplatin/pemetrexed for patients with locally advanced or metastatic non-small cell lung cancer whose disease has progressed with previous EGFR-TKI and whose tumours harbour a T790M mutation (LOGIK1604/NEJ032A).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21594-e21594
Author(s):  
Kentaro Tanaka ◽  
Hajime Asahina ◽  
Morihito Okada ◽  
Takahiro Uchida ◽  
Kana Watanabe ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Randomized Study ◽  
Small Cell ◽  
Combination Group ◽  
Small Cell Lung ◽  
First Line ◽  
Open Label ◽  
T790m Mutation ◽  
Egfr Tki

e21594 Background: Osimertinib is now available not only as a second line treatment for the patients with EGFR and T790M-mutation positive non-small cell lung cancer (NSCLC) after initial tyrosine kinase inhibitors (TKIs) but as a first line treantment for those who are TKI-naive. The efficacy and the safety of osimertinib plus palatinum-based chemotherapy has not yet been evaluated. Methods: This phase 2, open-label, randomized study enrolled adult patients (pts) with clinical stage IIIB or IV, or postoperative recurrent NSCLC harbouring susceptible EGFR and T790M mutations after preceded EGFR-TKI failure. Pts were randomly assigned to receive either an osimertinib [80 mg/day 1-21; q3w] or a combination of osimertinib [80 mg/day 1-21] with carboplatin/pemetrexed (hereafter combination) [area under the curve (AUC) = 5 and 500 mg/m2 day 1; q3w]. The primary endpoint was progression-free survival (PFS). Secondary endpoints included incidence of adverse events, response rate and overall survival. As indiction of osimertinib was expanded to a first line, we amended the protocol to discontinue the enrollment and perform final analyses. Results: From October 2016 to January 2019, 62 pts were enrolled [31 pts osimertinib; 31 pts combination] (median age 68 (37-80); 53.2% male; 83.3% stage IV; 100% adenocarcinoma; 59.7% exon 19 deletion and 40.3% L858R; 45.2% never smoker). The rate of grade (G) ≥ 3 treatment-related adverse events was 32.2% in the osimertinib group and 83.9% in the combination group. Neutropenia, anemia and thrombocytopenia were more common in the combination group and the rates of G ≥ 3 were 0%, 0% and 6.4% in the osimertinib group and 38.7%, 25.8% and 29.1% in the combination group, respectively. Three episodes (9.7%) of G ≥ 3 infection and one episode (3.2%) of G ≥ 3 febrile neutropenia were uniquely observed in the combination group, however, these were well managed. Two episodes (6.5%) of G ≥ 3 pneumonitis was observed only in the osimertinib group. Exaggeration of adverse events specific for osimertinib or any unknown adverse event was not observed in the combination group. Final PFS analysis is to be demonstrated in the presentation. Conclusions: Combination of osimertinib with carboplatin and pemetrexed demonstrated safety in patients with EGFR and T790M mutation-positive NSCLC and the efficacy should be validated in the future phase 3 study. Clinical trial information: 000024438.

The efficacy and safety of EGFR-TKI combined with chemotherapy in NSCLC patients with EGFR co-mutation with other oncogenic alterations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21077-e21077
Author(s):  
Wenhua Zhao ◽  
Wei Jiang ◽  
Hongtu Qiu ◽  
Aiping Zeng ◽  
Xiangqun Song ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Monotherapy Group ◽  
Efficacy And Safety ◽  
Observation Study ◽  
Primary Resistance ◽  
Nsclc Patients ◽  
Egfr Tki

e21077 Background: Previous studies indicated primary resistance to EGFR-TKIs might occur in EGFR co-mutation with other oncogenic alterations. However, the optimal therapeutic regimen for advanced NSCLC with EGFR co-mutation was still unknown. This respective observation study aimed to assess the efficacy and safety of the combination therapy with EGFR-TKI and chemotherapy in this sub-population. Methods: In this retrospectively study, from March 2017 to November 2019 advanced NSCLC patients with EGFR mutation detected using next-generation sequencing targeting 59 genes were screened for eligibility. We included patients of EGFR co-mutation with other oncogenic alterations receiving EGFR-TKI monotherapy or TKI plus chemotherapy as first-line therapy. The primary outcome was objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Disease control rate (DCR) and safety profile were considered to be the secondary endpoints. Results: Total 48 patients were enrolled. Among patients with concomitant mutation, the combination of chemotherapy with TKI was found to prolong mPFS (12.5 vs 7.3 months; HR, 0.38; 95%CI: 0.17-0.81; P = 0.012) compared with TKI monotherapy, with a trend of longer mOS (27.0 vs 22.4 months; HR, 0.40; 95%CI: 0.15-1.05; P = 0.062) and higher ORR (68.4% vs 44.8%, P = 0.113). The DCR were 100% in combination group and 93.1% in monotherapy group (P = 0.99). A proportion of 13.8% patients reported grade≥3 treatment-related adverse events in monotherapy group and 36.8% in combination group. Conclusions: EGFR co-mutation with other oncogenic alterations associated with poor treatment outcome with EGFR-TKI monotherapy. The combination of EGFR-TKI and chemotherapy was effective in this sub-population and side-effects were tolerable. The outcomes of this study should be confirmed by prospective clinical trials in future.

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 &lt; 0.00001) and objective response rate (ORR) (RR, 1.23; 95% CI, 1.13–1.34; P &lt; 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 &lt; 0.00001) and diarrhea (RR, 0.43; 95% CI, 0.30–0.60; P &lt; 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.

scholarly journals Comparative Efficacy and Safety of Immunotherapy Alone and in Combination With Chemotherapy for Advanced Non-small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xue Wang ◽  
Xiaomin Niu ◽  
Na An ◽  
Yile Sun ◽  
Zhiwei Chen
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Previous Treatment ◽  
Small Cell ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
Treatment Scenario ◽  
Nsclc Patients

There is a lack of direct cross-comparison studies in clinical trials between immunotherapy alone and combination treatment, especially in Non-Small Cell Lung Cancer (NSCLC) patients with high PD-L1 expression. To determine if anti-PD-(L)1 antibody combined with chemotherapy is more efficient than immune checkpoint inhibitor (ICI) monotherapy for advanced NSCLC patients in the real-world data. We retrospectively collected 325 patients with advanced NSCLC treated with ICI alone with or without chemotherapy from 11th July 2016 to 26th May 2020 to investigate which treatment scenario is the most efficient, and how clinical factors impact response. Patients with advanced NSCLC were treated with ICI monotherapy (178/325, 54.8%) or in combination with chemotherapy (147/325, 45.2%). The objective response rate and disease control rate were higher in the combination group than the monotherapy group. Patients (including those with distant metastasis) treated with chemo-immunotherapy were associated with a significantly longer median PFS and OS compared with the monotherapy group, irrespective of the PD-L1 expression level and previous treatment lines. No significant increase in the risk of immune-related adverse events (irAEs) was found after combination with chemotherapy (50.6 vs. 57.8%). IrAEs predicted better PFS of immunotherapy in the monotherapy group, especially for patients with late irAEs (after ≥4 cycles). Collectively, we demonstrated that ICI monotherapy plus chemotherapy might have better anti-tumor activity and an acceptable side-effect profile regardless of PD-L1 level or previous treatment lines. Both regimens were well-tolerated and cost-effective, the more efficient is usually recommended.

Safety and efficacy results of a phase IV, open-label, multicenter, safety-monitoring study of icotinib in treating advanced non-small cell lung cancer (NSCLC): ISAFE study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19161-e19161 ◽  
Author(s):  
Fenlai Tan ◽  
Aiqin Gu ◽  
Yiping Zhang ◽  
Shun Chang Jiao ◽  
Chang-li Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Safety Monitoring ◽  
Small Cell ◽  
Small Cell Lung ◽  
Open Label ◽  
Safety And Efficacy ◽  
Monitoring Study ◽  
Nsclc Patients

e19161 Background: The phase III ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS), based on which icotinib was approved by State Food and Drug Administration of China. We conducted a safety-monitoring study to assess the safety and efficacy of icotinib in a broad range of patients with advanced non-small-cell lung cancer (NSCLC) across China. Methods: This study was a single-arm, open-label, multi-center trial in advanced NSCLC patients who were suitable for treatment with oral icotinib 125 mg three times daily. Endpoints included safety, objective response rate (ORR) and disease control rate (DCR), were investigated overall and in subgroups. EGFR mutation analysis was performed retrospectively. Results: Between August, 2011 and August, 2012, 6,087 advanced NSCLC patients were registered with a median age of 63 years (range: 21-95 years), and 5,549 patients were evaluable for safety and tumor response. Baseline characteristics (%) were: male/female 50.8/49.2; non-smoker/ex- or current-smoker/no data 67.2/32.7/0.1; adenocarcinoma/non-adenocarcinoma/other 78.6/15.4/6.0; stage IIIB/IV/other 7.4/90.2/2.4; and 1,571(28.3%) patients were ≥ 70 years of age. The overall incidence of drug-related adverse events (AEs) of any grade was 31.5%, in which the most common drug-related AEs including rash (17.4%) and diarrhea (8.5%), and 3 patients experienced with interstitial lung disease (ILD) associated with icotinib. ORR and DCR were 30.0% and 80.6%, respectively. The safety in the elder patients (age ≥70, n=1,571) were similar to that in the overall population, the incidence of drug-related AEs of any grade was 30.6%, most of which were grade I or II. Among 989 patients who undertook EGFR mutation detection, 738 (74.6%) patients were mutation-positive with an ORR of 49.2% and a DCR of 92.3%. Moreover, in 251 (25.4%) wild type patients, the ORR and DCR were 17.8% and 75.7%, respectively. Conclusions: The data from over 6,000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated efficacy and a favorable toxicity profile in the routine clinical setting.

Detect T790M in cell free tumor DNA of Chinese advanced non-small cell lung cancer adenocarcinoma patients by different platforms and evaluate clinical outcomes of T790M positive patients with osimertinib monotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9104-TPS9104
Author(s):  
Zhiyong Liang ◽  
Ying Cheng ◽  
Yuan Chen ◽  
Weiping Liu ◽  
You Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Digital Pcr ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Tumor Dna ◽  
Egfr T790m

TPS9104 Background: EGFR T790M mutation occurs in approximately 50-60% of non-small cell lung cancer adenocarcinoma (NSCLC) patients with acquired EGFR-TKI resistance, based on tumor re-biopsies using an invasive clinical procedure. Recently, Cell free tumor DNA (ctDNA) has emerged as a specific and sensitive blood-based biomarker and studies have demonstrated ctDNA as a feasible and minimally invasive alternative to tissue biopsy. Data on different technology platforms used for EGFR T790M detection in blood in China is limited. We aim to compare the methods currently available in hospital practise, including cobas EGFR Mutation Test (Roche Molecular Systems), super-ARMS, digital PCR and NGS, to compare each platform and clinically validate each as companion diagnostic to osimertinib. Methods: This is an open-label, multi-center study in 250 locally advanced or metastatic NSCLC patients with documented EGFR sensitizing mutation and progression on previous EGFR-TKI. T790M mutation in plasma ctDNA will be tested by four methods: cobas, super-ARMS, digital PCR and NGS in order to evaluate the concordance, sensitivity and specificity of T790M testing in plasma between the cobas test and the other platforms. T790M positive patients by any of the four platforms will receive osimertinib treatment (administered orally as one 80 mg tablet once a day in ASTRIS study, NCT02474355) and the clinical outcomes (PFS, ORR, OS) will be followed. Patients will continue to receive osimertinib until disease progression (PD), as assessed by investigators. Digital PCR and NGS will be used to monitor the molecular evolution of T790M and C797S in plasma from NSCLC patients during osimertinib treatment. NGS will also be used to explore acquired resistance mechanisms before osimertinib treatment and after PD. 23 of planned 250 patients have been enrolled in the study as of January 2017. Clinical trial information: NCT02997501.

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