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Wei Nie
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Lunch & Poster Display session (ID 58)
- Event: ELCC 2019
- Type: Poster Display session
- Track:
- Presentations: 5
- Moderators:
- Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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131P - Upfront whole brain radiotherapy for multiple brain metastases in patients with EGFR-mutant lung adenocarcinoma (ID 268)
12:30 - 13:00 | Author(s): Wei Nie
- Abstract
Background
This study aimed to evaluate the efficacy of upfront whole-brain radiotherapy (WBRT) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with multiple brain metastases (BM).
a9ded1e5ce5d75814730bb4caaf49419 Methods
195 patients with EGFR mutations who had multiple BM at preliminary diagnosis were included and retrospectively reviewed in this study. Patients were administered for following treatments in a multi-disciplinary setting: upfront WBRT followed by EGFR-TKI, concurrent EGFR-TKI and WBRT and upfront EGFR-TKI followed by WBRT. A disease specific graded prognostic assessment (GPA) was performed for all the patients. The treatment response and overall survival (OS) were evaluated.
20c51b5f4e9aeb5334c90ff072e6f928 Results
The median OS of these patients was 27 months. Objective response rate (ORR) was much better in upfront WBRT group than other two groups (P = 0.004). Moreover, patients receiving upfront WBRT (n = 67) had longer OS than the concomitant group (36 vs. 25 months; P = 0.006) and the upfront EGFR-TKI group (36 vs. 25 months; P < 0.0001). The prognosis of patients with different GPA scores significantly differed (p < 0.0001). In subgroup of concomitant and upfront EGFR-TKI groups, patients with higher GPA scores (2-3) had more favorable prognosis compared with those with lower scores (0-1.5) (27 versus 25 months; P = 0.023). Patients receiving EGFR-TKI concurrently with WBRT had superior OS than those receiving upfront EGFR-TKI with high GPA scores. (37 versus 17 months; P = 0.023).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
The use of upfront WBRT in EGFR-mutated lung adenocarcinoma patients with multiple BM improves ORR and OS. More importantly, patients with high GPA scores are recommended to receive WBRT soon after EGFR-TKI therapy.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
National Natural Science Foundation of China (No.81502450) and Science and Technology Commission of Shanghai Municipality, China (No.18441904700).
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
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142P - Clinical management of advanced lung adenocarcinoma with ALK rearrangement: Real-world treatment outcomes and long-term survival (ID 546)
12:30 - 13:00 | Author(s): Wei Nie
- Abstract
Background
Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have been demonstrated to be effective in ALK-rearranged, advanced lung adenocarcinoma patients. However, data from a real-world setting is very limited. The aim of the study was to: a) determine long-term survival in these patients and investigate factors associated with their prognosis; and b) analyze the clinical outcomes of patients who were sequentially treated with next-generation ALK-TKIs.
a9ded1e5ce5d75814730bb4caaf49419 Methods
ALK-rearranged, advanced lung adenocarcinoma patients who were treated with crizotinib were included between January 2013 and December 2016. Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. The hazard ratio (HR) for the risk of progression or death was calculated using multivariate Cox regression model.
20c51b5f4e9aeb5334c90ff072e6f928 Results
A total of 5286 patients were screened and 176 eligible patients were included. Median PFS and OS were 12.4 months (95% CI, 10.3-14.6 months) and 45.6 months (95% CI, 37.6-53.7 months), respectively. 36.3% of patients were 5-year survivors. Extrathoracic metastasis before crizotinib treatment was independently associated with worse PFS (HR, 1.77, 95% CI, 1.24-2.53, P < 0.01) and OS (HR, 1.61, 95% CI, 1.02-2.54, P = 0.04). 45 patients were sequentially treated with newer-generation ALK-TKIs, obtaining a statistically longer OS (54.8 months, 95% CI, not calculable) than patients who were solely treated with crizotinib during clinical management (36.6 months, 95% CI, 29.2-43.9 months, P < 0.01).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Our study provides useful information about ALK-rearranged, advanced lung adenocarcinoma patients treated with ALK-TKIs in a real-world setting.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
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170P - Advanced non-small cell lung cancer patients with low tumor mutation burden might derive benefit from anti-programmed cell death (PD)-1 and anti-programmed deathligand 1 (PD-L1) blockade (ID 194)
12:30 - 13:00 | Presenting Author(s): Wei Nie
- Abstract
Background
We aimed to investigate the association between tumor mutation burden (TMB) and survival in non-small cell lung cancer (NSCLC) patients with anti–programmed cell death (PD)-1 and anti--programmed cell deathligand 1 (PD-L1) blockade.
a9ded1e5ce5d75814730bb4caaf49419 Methods
Five retrospective cohorts using PD1/PDL1 blockades and The Cancer Genome Atlas (TCGA) lung cancer data set were included in this study. The restricted cubic spline (RCS) analysis was used to explore the association between TMB and survival. The cut-off values for TMB were determined by X-tile software. Primary outcomes were overall survival (OS) and progression-free survival (PFS). The associations between TMB and intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, and T cell populations were also investigated.
20c51b5f4e9aeb5334c90ff072e6f928 Results
TMB showed an inverted J-shaped curve with survival risk in RCS plot. Two cut-off values were determined by X-tile software in each cohort. In addition to high TMB, low TMB was an independent prognostic indicator for OS and PFS in NSCLC patients treated with PD1/PDL1 blockades. Objective response rate (ORR), disease control rate (DCR), and 1-year OS rate in the low TMB group were higher than that in the medium TMB group. In TCGA lung cancer data set, low TMB was also associated with longer OS in comparison with medium TMB. Furthermore, NSCLC patients with low TMB had significantly lower intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, T helper type 2 (Th2) cells, and CD8+ T cells, but higher levels of Th1 and Th17 cells.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
NSCLC patients with low TMB might benefit from anti-PD1/PDL1 immunotherapy.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
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190P - ERGR-TKIs combined with chemotherapy delays intracranial progression in EGFR-mutant lung adenocarcinoma patients (ID 269)
12:30 - 13:00 | Author(s): Wei Nie
- Abstract
Background
The aim of this study was to evaluate if the combination of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) plus chemotherapy could delay the presence and decrease the incidence of brain metastases (BM) in patients with EGFR-mutant advanced lung adenocarcinoma.
a9ded1e5ce5d75814730bb4caaf49419 Methods
100 eligible patients who developed BM were retrospectively reviewed. Patients received treatment with either EGFR-TKI monotherapy or EGFR-TKI plus chemotherapy. Intracranial progression-free survival (iPFS), systemic progression-free survival (PFS) and overall survival (OS) were evaluated.
20c51b5f4e9aeb5334c90ff072e6f928 Results
The median OS in the whole group was 37 months (interquartile range 6 to 94 months). Patients treated with EGFR-TKI plus chemotherapy had longer PFS compared with EGFR-TKI alone (16 vs. 10 months;
fd69c5cf902969e6fb71d043085ddee6 ConclusionsP =0.030). Moreover, addition of chemotherapy showed an obvious iPFS advantage over EGFR-TKI alone (21 vs. 14 months;P =0.026). In all initial progression, less patients in the combination group developed BM compared to patients treated with EGFR-TKI monotherapy (15 vs. 27,P =0.002), with a hazard ratio (HR) of 0.64 (95% CI, 0.43−0.96) for BM in the combination group versus the EGFR-TKI monotherapy group.
The combination of EGFR-TKI plus chemotherapy demonstrated prolonged iPFS as well as PFS and reduced the occurrence and progression risk of intracranial metastases compared to EGFR-TKI monotherapy. EGFR-TKI plus chemotherapy is recommended for lung adenocarcinoma patients with EGFR-sensitive mutations.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Science and Technology Commission of Shanghai Municipality, China (No.18441904700).
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
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91P - Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns (ID 273)
12:30 - 13:00 | Author(s): Wei Nie
- Abstract
Background
Lung cancer diagnosed solely with intrathoracic metastases are classified as M1a, but intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the survival difference between different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations.
a9ded1e5ce5d75814730bb4caaf49419 Methods
EGFR-mutant patients diagnosed only with intrathoracic metastasis between March 2011 and October 2016 were collected. Prognosis was analyzed according to metastatic patterns based on univariate and multivariate analysis.
20c51b5f4e9aeb5334c90ff072e6f928 Results
A total of 137 patients (60 patients who only had pleural metastasis [Group A], 44 patients who only had contralateral lung metastasis [Group B] and other 33 patients had both pleural and contralateral lung metastasis with or without pericardial effusion [Group C]) were included in the study. The median OS (overall survival) times were 38.1(95%confidence interval [CI]: 27.8-48.4), 35.7(95%CI: 23.4-48.0), and 29.7(95%CI: 22.8-36.6) months for Group A, Group B, and Group C, respectively (p = 0.037). Multivariate analysis demonstrated that Group A and Group B had longer OS than Group C (hazard ratio [HR]=0.524, 95%CI: 0.307-0.894, p = 0.018; HR = 0.473, 95%CI: 0.241-0.931, p = 0.030, respectively) among lung adenocarcinoma patients with EGFR mutation. With regard to patients with pleural or contralateral metastasis only, OS benefit (p = 0.579) was not significant between the two groups. Subgroup analysis demonstrated that the OS benefit of Group A was significant in patients with N0-1 disease and 21L858R mutant but not in EGFR exon 19 deletion, N2-3 stage and T3-4 stage disease patients.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
The prognosis of EGFR-mutant lung adenocarcinoma patients diagnosed only with intrathoracic metastasis is different, indicating that M1a may should be refined in the future.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
National Natural Science Foundation of China (No.81502450) and Science and Technology Commission of Shanghai Municipality, China (No.18441904700).
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25
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Mini Oral session II (ID 63)
- Event: ELCC 2019
- Type: Mini Oral session
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 4/11/2019, 16:40 - 17:40, Room C
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117O - Racial disparities in characteristics and prognosis in Asian versus white patients receiving atezolizumab: An ancillary analysis of POPLAR and OAK studies (ID 339)
16:40 - 17:40 | Author(s): Wei Nie
- Abstract
- Presentation
Background
Racial differences in characteristics and prognosis of Asiatic and White patients receiving immunotherapy have not been well described.
a9ded1e5ce5d75814730bb4caaf49419 Methods
We studied 390 patients from the POPLAR and OAK studies who received atezolizumab with evaluable biomarker parameters retrieved from a subsequent blood-based study. The differences of Asians versus Whites in baseline characteristics, outcomes and genetic mutations of atezolizumab therapy were assessed.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Asiatic and White patients differed in characteristics including smoking history, baseline sum of the longest diameters (BLSLD), EGFR mutation frequency, programmed death-ligand 1 (PD-L1) expression and blood-based tumor mutational burden (bTMB) level. Overall survival (OS) was longer in Asians compared with Whites before (median OS: 18.7 vs. 11.1 mo; P = 0.005) and after (median OS: 20.9 vs. 12.6 mo; P = 0.005) propensity score matching (PSM). Race was an independent prognostic factor for OS (Asian vs White: HR 0.647, 95% CI 0.447-0.936, P = 0.021) in addition to performance status (PS), histology, BLSLD, and number of metastatic sites. The objective response rate (ORR) for Asians and Whites was 8.2% and 17.1%, respectively and disease control rate (DCR) was 51.2% and 47.7%, respectively. The blood-based mutational landscape differentiated between Asians and Whites. In the overall population, mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response while mutations of TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 were associated with OS. Comparing the frequency of efficacy- or prognosis- related mutations, Asians had more EGFR mutations and less TP53 and STK11 mutations than Whites.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Asians and Whites differed in the clinicopathological features and mutational landscape which may explain the superior efficacy of atezolizumab in Asiatic patients with NSCLC. This study conveys implications for further studies on racial disparity in the treatment of immunotherapy.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Support (No. 20161434).
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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118O - Blood tumor mutational burden as a predictor of clinical benefit in non-small cell lung cancer patients treated with docetaxel: Secondary analysis of the OAK and POPLAR randomized clinical trials (ID 222)
16:40 - 17:40 | Presenting Author(s): Wei Nie
- Abstract
- Presentation
Background
Blood-based tumor mutational burden (bTMB), which is measured by targeted next-generation sequencing (NGS) using cell-free DNA (cfDNA), shows a positive correlation with tissue-based TMB and is a predictive biomarker for non-small cell lung cancer (NSCLC) patients receiving atezolizumab. However, the role of bTMB in other treatment settings, such as chemotherapy, is unknown. We hypothesized that advanced NSCLC patients with low bTMB would derive more benefit from chemotherapy.
a9ded1e5ce5d75814730bb4caaf49419 Methods
The clinical and genetic data from docetaxel arm of OAK trial (n = 318, training cohort) and POPLAR trial (n = 106, validation cohort) were used. The FoundationOne CDx NGS assay was used to quantify bTMB. Efficacy was determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Durable clinical benefit (DCB) was defined as overall survival (OS) that last more than 12 months. Gene alterations and bTMB were compared among patients with DCB and no durable benefit (NDB). The cut-off value of bTMB for predicting OS was determined by time-dependent receiver operating characteristic (ROC) curve.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Significantly lower bTMB was observed in DCB than NDB (median, 5 vs 9 SNVs/Mb; P < 0.001) and in patients with partial response (PR) versus stable disease (SD) versus progressive disease (PD) (median, 5 vs 7 vs 10 SNVs/Mb; P = 0.007). The optimised cut-off value of bTMB for predicting OS was 7 SNVs/Mb by time-dependent ROC curve. In training cohort, the median OS of patients with low bTMB was 11.5 months and 6.4 months for those with high bTMB (HR 0.638; 95% CI 0.497-0.820; P < 0.001). The median PFS in the low bTMB group (4.3 months) was significantly longer than that in the high bTMB group (2.9 months; HR 0.588; 95% CI 0.466-0.742; P < 0.001). These results were confirmed in validation cohort. Variants in EGFR and KEAP1 associated with DCB and NDB, respectively.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Our data showed that low bTMB (≤ 7 SNVs/Mb) was a clinically biomarker for docetaxel treatment in NSCLC.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
