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Jianxing He
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MA08 - Clinical Trials in Brain Metastases (ID 906)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 203 BD
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MA08.03 - EGFR-TKI Plus Brain Radiotherapy Versus EGFR-TKI Alone in the Management of EGFR Mutated NSCLC Patients with Brain Metastases: A Meta-Analysis (ID 12990)
15:25 - 15:30 | Author(s): Jianxing He
- Abstract
- Presentation
Background
It has been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) presented better efficacy than brain radiotherapy (brain RT) in the treatment of brain metastasis (BM) in EGFR mutated NSCLC patients. However, whether the combination of EGFR-TKI and brain RT is better than EGFR-TKI alone remains unclear. We aim to compare the benefit of adding brain RT to EGFR-TKI by a meta-analysis of currently available data.
a9ded1e5ce5d75814730bb4caaf49419 Method
A systematic search for relevant articles was conducted in six databases (PubMed, EMBASE, Cochrane database, Medline, Web of Science, Google scholar). The primary outcome was overall survival (OS) between groups, and the secondary outcome was intra-cranial progression-free survival (icPFS), both being measured as hazard ratios (HRs). The data was synthesized by random-effects model using STATA 13.0.
4c3880bb027f159e801041b1021e88e8 Result
A total of four retrospective studies involving 507 EGFR mutated patients with BM at the first diagnosis were included, 209 patients received brain RT (predominantly whole brain RT). Combined therapy of EGFR-TKI and brain RT reduced 19% risk of deaths (OS HR=0.81, 95% CI 0.53-1.26; P=0.36) and 16% risk of intracranial progression (icPFS HR=0.84, 95% CI 0.55-1.27; P=0.40) compared with EGFR-TKI alone, however, no statistically significance was observed. Further subgroup analyses suggested that patients with 21 exon L858R mutation were more inclined to have greater icPFS benefit under combination therapy (HR 0.67, 95% CI 0.19-2.40) in contrast to 19 exon deletion patients (HR 1.35, 95% CI 0.88-2.09). In addition, patients older than 65 (HR 0.74, 95% CI 0.37-1.48) might benefit more from combination than those younger than 65 (HR 4.47, 95%CI 0.29-70.13).
8eea62084ca7e541d918e823422bd82e Conclusion
This meta-analysis suggested that the combination of EGFR-TKIs and brain radiotherapy showed similar but potentially better OS and intracrnial control in EGFR-mutated NSCLC patients when compared to EGFR-TKI alone, especially for those with L858R mutations or older than 65. The current results underscore the importance of future randomized control trials and provide information for study design.
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MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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MA15.05 - The Mutational Profiles of EGFR 19 Exon Deletion and 21 Exon L858R Mutation and Their Association with Primary Response to EGFR-TKIs (ID 12671)
14:00 - 14:05 | Author(s): Jianxing He
- Abstract
- Presentation
Background
In addition to the known resistant genetic alterations, such as de novo T790M and TP53 mutations, some recent studies suggested that other concomitant mutations might also compromise the efficacy of EGFR-TKIs. Meanwhile, it has been widely observed that EGFR 19 exon deletion (19del) was associated with better outcomes in treatments with EGFR-TKIs than L858R mutation (L858R). It is of interest to explore whether the respective mutational profiles of 19del and L858R may explain their different sensitivity to EGFR-TKIs.
a9ded1e5ce5d75814730bb4caaf49419 Method
We obtained individual patient data from 7 studies (including 1 from our center) using next generation sequencing to comprehensively determine the mutational profile of EGFR mutated patients. As different panels were used by different studies, we analyzed T790M, TP53 and the loci that were reported by at least 4 studies (half of the included ones).
4c3880bb027f159e801041b1021e88e8 Result
A total of 250 19del and 279 L858R patients were included. We found similar prevalence of all co-mutations (19del 65.2% vs. L858R 64.2%), TP53 (19del 36.8% vs. L858R 40.9%), APC, BRAF, PIK3CA, STK11, PDGFRA, PTEN, AKT1 and KIT between the two types, except for de novo T790M (19del 34.4% vs. L858R 50%, P=0.07), CDKN2A (19del 10.5% vs. L858R 3.4%, P=0.03) and KRAS (19del 0.5% vs. L858R 4.0%, P=0.01). In addition, the number of co-mutations was equivalent between the two types (19del 0.95±0.95 vs. L858R 0.93±0.90, P=1.00). Through multivariate logistic regression, we found that EGFR mutation type, de novo T790M, TP53 and other co-mutations, all had independent adverse effects on primary response rate. Consistently, we found that in those without co-mutations, 19del still showed better outcomes compared with L858R (pure EGFR mutations: 19del 88.0% vs. L858R 68.4%), and that the response rates in both mutation types decreased in the same extent when contaminated with other mutations (EGFR mutations with co-mutations: 19del 53.1% vs. L858R 30.0%).
8eea62084ca7e541d918e823422bd82e Conclusion
Our study demonstrated that the presence of T790M, TP53 and other concomitant mutations indicated poor response to EGFR-TKIs, but most of them showed similar prevalence between 19del and L858R. Patients with L858R showed significantly less response than those with 19del regardless of the co-mutation status, indicating that some intrinsic factors and potentially de novo T790M, rather than other co-mutations, might underlie the different sensitivity of 19del and L858R to EGFR-TKIs.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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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OA13 - Therapeutics and Radiation for Small Cell Lung Cancer (ID 927)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 10:30 - 12:00, Room 203 BD
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OA13.03 - Anlotinib as Third-Line or Further-Line Treatment in Relapsed SCLC: A Multicentre, Randomized, Double-Blind Phase 2 Trial (ID 12102)
10:50 - 11:00 | Author(s): Jianxing He
- Abstract
- Presentation
Background
Treatment for patients with relapsed small cell lung cancer (SCLC) who failed ≥ 2 lines of chemotherapy have high unmet needs. Anlotinib is a novel TKI with highly selective inhibition effects on multi-targets, especially on VEGFR, c-Kit, PDGFR, FGFR. Here we report results of a phase 2 study of anlotinib for the third-line and further-line treatment of SCLC. (ALTER1202, NCT03059797).
a9ded1e5ce5d75814730bb4caaf49419 Method
Eligible either limited- or extensive-stage SCLC patients with disease progression after ≥ 2 lines of chemotherapy were randomized 2:1 to anlotinib or placebo (12 mg PO QD from day 1 to 14, every 3 weeks). The primary endpoint was PFS and secondary endpoints was OS, ORR, DCR, quality of life and safety.
4c3880bb027f159e801041b1021e88e8 Result
Between March 2017 and May 2018, 120 patients from 11 centers were randomized to either anlotinib arm (n=82) or placebo arm (n=38). Until the data cutoff date (30 Jun 2018), median PFS was 4.1 months (95%CI, 2.8 to 4.2 months) in anlotinib arm and 0.7 months (95% CI, 0.7 to 0.8 months) in placebo arm (HR, 0.19; 95% CI, 0.12 to 0.32, p<0.0001). OS data were not sufficiently mature for analysis. Although ORR was similar, considerable improvement in DCR was observed in anlotinib arm (71.6% vs 13.2%, p<0.0001). Treatment-related adverse events (TRAEs) occurred more frequently in anlotinib arm than that in placebo (87.7% and 74.4%). The most common TRAEs were hypertension, anorexia, fatigue, and hand-foot syndrome. Grade ≥3 TRAEs occurred in 29 (35.8%) of patients in anlotinib arm and 6 (15.4%) in placebo arm, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
ALTER 1202 study demonstrates anlotinib should be considered a treatment option for patients with relapsed SCLC who have experienced treatment failure with two lines of chemotherapy. The safety profile was consistent with the previous report and no newly adverse events were identified.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-107 - The Impact of Anlotinib on Quality of Life in Patients with Advance NSCLC: Post-Hoc Analysis of a Phase III Randomized Control Trial (ALTER0303) (ID 12249)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD α/β, c-Kit and Ret. In the phase Ⅲ ALTER-0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non-small-cell lung cancer (NSCLC) patients who had received at least two previous chemotherapy and epidermal growth factor receptor /anaplastic lymphoma kinase targeted therapy regimens. This study assessed quality of life (QoL) in these patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. The QoL were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the associated EORTC Quality of Life Lung Cancer Specific Module (QLQ-LC13) at baseline, end of cycle 1, end of every two cycles, and at the final visit. The analyses were conducted in the first 6 cycles. Differences in scores of 10 points or more between two arms or from baseline were considered clinically meaningful.
4c3880bb027f159e801041b1021e88e8 Result
A total of 437 patients were assigned to anlotinib (n=294) and placebo (n=143). The completion rates of the QoL questionnaires were from 69.9 % to 97.0%. Mean scores of QLQ-C30 and QLQ-LC13 subscales were similar in the anlotinib and placebo arms at baseline. Compared to placebo, anlotinib improved role functioning (at cycle 2), social functioning (at cycle 4), dyspnea (at cycle 2, 4), insomnia (at cycle 6), constipation (at cycle 2) and financial problems (at cycle 2). Only sore mouth or tongue symptom was worse in the anlotinib arm (at cycle 2, 4, 6) than in the placebo arm.
8eea62084ca7e541d918e823422bd82e Conclusion
Anlotinib improved quality of life versus placebo in advanced NSCLC patients who had received at least two previous chemotherapies. The QoL analyses provided evidence that anlotinib should be a choice for the third-line treatment or beyond in advanced NSCLC.
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P1.01-108 - Management of Anlotinib-Related Adverse Events: Data From ALTER 0303 (ID 12054)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
Anlotinib is an oral tyrosine kinase inhibitor targeting VEGFR, FGFR, PDGFR and c-kit. In the phase Ⅲ ALTER-0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non-small-cell lung cancer (NSCLC) patients who had received at least two previous chemotherapy and epidermal growth factor receptor /anaplastic lymphoma kinase targeted therapy regimens. This study summarized adverse event management in this trial.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0) and managed by investigators. Adverse events and key strategies for preventing and managing the most common adverse events were described. Proportions were compared using the χ2 test or Fisher’s exact test, as appropriate. Two-sided values of P <0.05 were considered statistically significant. Analyses were calculated by SAS 9.4.
4c3880bb027f159e801041b1021e88e8 Result
Between February 2015, and August 2016, a total of 437 patients were randomized to anlotinib group (n=294) and placebo group (n=143). The most common anlotinb related adverse events were hypertension (64.6%), fatigue (46.3%), TSH elevation (44.6%), hand-foot syndrome (HFS) (43.2%), hypertriglyceridemia (38.8%), anorexia (38.4%). The most common anlotinib related grade ≥3 adverse events were hypertension (13.3%), HFS (3.7%), and hypertriglyceridemia (2.4%). The median onset time of hypertension, HFS, and hypertriglyceridemia were 6 days, 30 days, and 22 days respectively.
To monitor blood pressure, every patient had an electronic manometer. One hundred and eight (36.7%) patients received dihydropyridine calcium channel blockers, 79 (26.9%) patients received converting enzyme inhibitors of angiotensin /angiotensin receptor blockers, 57 (19.4%) patients received diuretics, 35 (11.9%) patients received beta-blockers. Only 3 (1.0%) patients need dose modification due to hypertension.
Prophylactic measures of HFS were recommended. Frequent emollients should be used on hands and feet to maintain skin hydration, manicure or pedicure to control calluses, protect pressure points and tender areas of feet with insole cushions, shock-absorbing soles, comfortable shoes. Seven (2.3%) patients required dose reduction due to hand-foot skin syndrome. Eleven (3.7%) patients received cortisone cream for topical therapy.
Twenty-four patients received fibrates to reduce plasma triglyceride level. Two (0.7%) patients required dose reduction due to hypertriglyceridemia.
8eea62084ca7e541d918e823422bd82e Conclusion
Anlotinb-related adverse events could be controlled by prophylactic measures, and early intervention.
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 4
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-35 - Sleeve Lobectomy Versus Pneumonectomy for Non-Small Cell Lung Cancer, a Cumulative Updated Meta-Analysis (ID 13668)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
Sleeve lobectomy (SL) is an appealing alternative to pneumonectomy (PN) for central or locally advanced non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the benefits of SL versus PN for NSCLC through cumulative meta-analysis.
a9ded1e5ce5d75814730bb4caaf49419 Method
A systematic review and cumulative analysis of comparative studies reporting both postoperative and survival outcomes of SL and PN was performed through a comprehensive search of PubMed, EMBASE and the Cochrane library electronic databases from inception to April 2018
4c3880bb027f159e801041b1021e88e8 Result
A total of 9153 patients (SL: 3658, PN: 5495) from thirty-two studies were included. Meta-analysis was conducted for hazard ratio (HR), postoperative mortality, postoperative morbidity, local recurrence, and overall survival. PN was inferior to SL in terms of hazard ratio (HR=0.66, 95% confidence interval [CI]=0.59 to 0.75, I2=56%). Lower postoperative mortality was found in SL group (OR=0.45, 95% CI=0.36 to 0.56, I2=0.0%). While SL and PN showed no significant difference in local recurrence (OR=0.86, 95% [CI]=0.69 to 1.07, I2=45.0%) or postoperative morbidity (OR=0.92, 95% [CI]=0.78 to 1.09, I2=29.0%). Moreover, the 1-, and 5-years survival rates (1-yr: OR=2.19, 95% CI=1.93 to 2.5, I2=14.0%) (5-yrs: OR=1.94, 95% CI=1.61 to 2.35, I2=52.0%) and survival in patients with pN0 or pN1 at 5-years (OR=1.79, 95% CI=1.19 to 2.67, I2=3.0%) in the SL group were significantly higher than that in the PN group. As demonstrated in our cumulative meta-analysis, these effects were consistent over the years.
8eea62084ca7e541d918e823422bd82e Conclusion
SL could be considered an acceptable alternative to PN for the treatment of NSCLC.
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P1.16-39 - A Nomogram for Predicting Survival Of TNM8 Stage I Non-Small Cell Lung Cancer Patients to Tailor Potential Chemotherapy Candidates (ID 12463)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
The 8th TNM stage I non–small-cell lung cancer (NSCLC) patients are not considered as candidates for adjuvant chemotherapy (ad-Chemo). This study aimed to develop a nomogram for predicting cancer specific survival (CSS) of these patients and identifying those who might benefit from ad-Chemo.
a9ded1e5ce5d75814730bb4caaf49419 Method
NSCLC cases between 1998 and 2013 were extracted from the SEER database and randomly divided into training and validation cohorts. We identified and integrated the recurrence-associated factors to build a nomogram. We determined the cut-off for the high-risk group by matching the nomogram-predicted 5-year CSS with that of the current 4-5 cm stage IIA cases. The difference in benefit from chemotherapy between risk groups was examined using both SEER and NCDB cohort.
4c3880bb027f159e801041b1021e88e8 Result
A total of 30,475 patients with stage I were included for analysis. Six independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The C-index of the nomogram was higher than that of the staging system (IA1, IA2, IA3, IB) (training set, 0.59 vs. 0.56, P < 0.01; validation set, 0.62 vs. 0.57, P < 0.01). Specifically, 26.9% stage IB patients (8.1% of all stage I) were categorized into the high-risk group (score>29) and had inferior CSS compared with stage IIA patients. In addition, chemotherapy was associated with significantly better OS (HR, 0.739; P = 0.047) than no-chemotherapy in the high-risk group.
8eea62084ca7e541d918e823422bd82e Conclusion
We established a practical and economical nomogram to predict CSS for 8th edition stage I NSCLC, and identified a subset of patients at relatively high risk for recurrence who might benefit from ad-Chemo.
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P1.16-41 - The Role of Surgery in Pulmonary Large Cell Neuroendocrine Carcinoma: A Propensity-Score Matching Analysis of SEER Database (ID 12772)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subset of non-small-cell lung cancer with poor prognosis. Due to its rarity, the optimal therapy strategy for pulmonary LCNEC remains undefined. We aimed to evaluate the role of surgery for stage I-III LCNEC using the Surveillance, Epidemiology, and End Results (SEER) database.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with stage I-III LCNEC were extracted from the SEER database (2004-2014). Propensity-score matching was performed to reduce the effect of potential confounders. Kaplan-Meier curves were constructed for overall survival (OS) and cancer-specific survival (CSS) for patient strata based on surgery use or nonuse. Multivariable Cox-regression was used to explore the efficacy of different treatment strategies.
4c3880bb027f159e801041b1021e88e8 Result
A total of 944 LCNEC patients were identified, of which 674 (71.4%) received surgery. Both OS and CSS of surgery use group were superior to surgery nonuse group in the whole cohort (HR=0.48, P<0.001 and HR=0.41, P<0.001, respectively). Among matched cohort, significantly greater benefits in OS and CSS (Figure 1) from surgery was observed in both stage I-II (HR=0.47, P=0.001 and HR=0.43 P<0.001, respectively) and stage III (HR=0.66, P=0.039 and HR=0.63, P=0.031, respectively). On multivariable analysis of surgical group, there was no significant difference in either OS or CSS between surgery alone and the addition of chemotherapy or (and) radiation for stage I-II patients, whereas favorable survival outcomes of surgery plus chemotherapy (OS: HR=0.26, P<0.001; CSS: HR=0.30, P=0.001) and surgery plus chemotherapy and radiation (OS: HR=0.33, P<0.001; CSS: HR=0.34, P=0.002) were significantly evident for stage III patients.
8eea62084ca7e541d918e823422bd82e Conclusion
This is the largest study exploring the benefit of surgery for stage I-III pulmonary LCNEC. Regardless of stage, surgery showed remarkable survival benefits for LCNEC patients. It is suggested that surgery alone may be sufficient for stage I-II, whereas the multimodal combination of surgery and other therapies should be considered for stage III disease.
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P1.16-48 - The Impact of Segmentectomy Versus Lobectomy on Pulmonary Function of Patients with Non-Small Cell Lung Cancer: A Meta-Analysis (ID 12839)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
Lobectomy (Lob) and lymph node dissection is considered as the standard surgical procedure for non-small cell lung cancer (NSCLC). Segmentectomy (Seg) has been recently regarded as an alternative in early peripheral NSCLC owing to its advantages of lung function reservation. Thus, we performed a meta-analysis with the aim of evaluating whether Seg offers a better lung functional advantage over Lob.
a9ded1e5ce5d75814730bb4caaf49419 Method
A comprehensive search of online databases was performed. Perioperative outcomes and lung functional index and were synthesized. The odds ratio (OR) or SMD and its 95% CI was calculated using a random effects model. Subgroup was conducted according to different time points. Single-arm meta-analysis was conducted for lung function at each visit time. Repeated-measures analysis of variance (ANOVA) was used to compare the lung function between at each visit.
4c3880bb027f159e801041b1021e88e8 Result
A total of 5 eligible studies including 958 patients were recruited. There were no significant differences according to baseline characteristics before surgery between groups (Seg and Lob). Seg correlated with a greater postoperative preserved pulmonary function than Lob in FVC (SMD=0.23, p=0.009) (Figure A) and FEV1 (SMD=0.27, p=0.002) (Figure B), especially before 12 months. ANOVA showed there were no differences between two groups in FVC (p=0.647) and FEV1 (p=0.468) according to each visit time (Figure C). Seg group showed significantly less postoperative complications compared with the Lob. (OR=0.64, p=0.045) and the recurrence rate were same between groups (OR=0.89, p=0.623).
8eea62084ca7e541d918e823422bd82e Conclusion
Seg offers a better lung functional preservation in short time and reduces postoperative complication compared with Lob. However, two groups showed no significant difference on lung function and tumor relapse according to long follow up.
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-01 - The Impact of Anlotinib on Brain Metastases of NSCLC: Post-Hoc Analysis of a Phase III Randomized Control Trial (ALTER0303) (ID 12454)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
Few evidence has measured the intracranial impact of multitargeted VEGFR-TKIs. Anlotinib hydrochloride, which targets VEGFR, PDGFR, FGFR and c-Kit, has been shown to significantly prolong PFS and OS compared with placebo as second/third-line treatment for NSCLC in a randomized, double-blind, phase Ⅲ trial (NCT02388919). Herein we sought to analyze anlotinib’s effect in managing brain metastases (BM) and its brain-associated toxicities.
a9ded1e5ce5d75814730bb4caaf49419 Method
The PFS/OS of anlotinib versus placebo in those with and without BM records at baseline were calculated and compared respectively. In addition, time to brain progression (TTBP), a direct indicator of intracranial control, was also compared between anlotinib and placebo. All calculations were adjusted for confounding factors, including stage, histology, driver mutation type, etc.
4c3880bb027f159e801041b1021e88e8 Result
A total of 437 patients (294 receiving anlotinib; 143 receiving placebo) were included. 97 cases (22.2%) were recorded to have BM at baseline. There were more BM cases among younger patients and those with adenocarcinoma. Both of the benefit magnitude from anlotinib over placebo were similar between BM and non-BM group in terms of PFS (BM: HR 0.19, 0.11-0.34; non-BM: HR 0.29, 0.22-0.37; interaction P=0.691) and OS (BM: HR 0.71, 0.44-1.16; non-BM: HR 0.67, 0.51-0.89: interaction P=0.789). More specifically, anlotinib was associated with significantly longer TTBP (HR 0.11, 95% CI 0.03-0.41, P=0.001; Figure1) despite all confounders, indicating a 90% reduction of brain progression risk from anlotinib. Interestingly, anlotinib was also associated with more neural toxicities (18.4% vs. 8.4%, P=0.007) and psychological symptoms (49.3% vs. 35.7%, P=0.008) compared with placebo, especially headache (P=0.01), brain edema (P=0.04) but not infarction or cerebral hemorrhage. The above results were all confirmed both in intention-to-treat and per-protocol population.
8eea62084ca7e541d918e823422bd82e Conclusion
Anlotinib can benefit NSCLC patients with brain metastases and is highly potent in managing intracranial lesions. Its special effect on brain metastases and cerebral tissues merits further investigation.
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P2.01-110 - Unique Genomic Profile Revealed by Malignant Pleural Effusion (ID 13590)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
The accumulation of malignant pleural effusion (MPE), often occurring in advanced lung cancer patients, is the result of pleural space invasion by malignant cells, which disrupt the drainage of pleural fluid. Numerous studies have confirmed the clinical utility of MPE for mutation detection from single gene perspective, often focusing on classic driver genes. Very few studies have interrogated MPE as a media for liquid biopsy using targeted sequencing. In this study we investigated the potential of using MPE as a media for liquid biopsy using targeted sequencing.
a9ded1e5ce5d75814730bb4caaf49419 Method
Matched plasma and MPE samples were obtained from 154 patients with advanced NSCLC. Among them, 17 patients had matched primary tissue sample and MPE precipitates. Ultra-deep targeted sequencing using a panel consisting of 168 lung cancer-related genes, spanning 160 kb of human genome was performed with an average sequencing depth of 10,000x for MPE and 1,000x for tissue samples.
4c3880bb027f159e801041b1021e88e8 Result
Using tissue sample as a reference, detection rates of driver mutations in MPE cfDNA (supernatant), MPE precipitates and plasma are 100%, 70.6% and 82.3%, respectively. The median maximum allelic fractions (MAF) for MPE cfDNA, precipitates and plasma are 12.9%, 14.8% and 3.6%, respectively. MPE and tissue have comparable median MAF, which is significantly higher than plasma (p=0.01), demonstrating the superiority of MPE cfDNA in mutation detection. Next, we compared and contrast genomic profiles derived from MPE cfDNA and plasma cfNDA. Collectively, in 154 patients, we identified 939 variants from MPE and 865 variant from plasma; among them, 770 variants were shared by the two media; 169 variants were MPE specific and 95 variants were plasma specific. EGFR and TP53 are the two most frequently occurring mutations in both MPE cfDNA and plasma cfDNA. MPE cfDNA of 56 patients had CNVs detected; in contrast, only 27 patients had CNVs detected from plasma sample, resulting in a significantly higher detection rate in MPE cfDNA (p<0.01). Collectively, we identified 201 CNVs; among them, 164 were shared by both media; 33 are MPE specific and the remaining 4 are plasma specific.
8eea62084ca7e541d918e823422bd82e Conclusion
Collectively, our study demonstrates superiority of MPE cfDNA as an alternative media for liquid biopsy. In addition to higher detection rate and MAF, MPE cfDNA also revealed a unique genomic profile, especially in capturing CNV.
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P2.10 - Prevention and Tobacco Control (Not CME Accredited Session) (ID 959)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.10-17 - Environmental Tobacco Smoke Exposure and EGFR Mutations in Non-Smokers with Lung Cancer: A Dose-Response Analysis of Published Data (ID 12458)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
Tobacco smoke is a well-known strong mutagen. However, as EGFR mutations (EGFRmut) in lung cancer were predominantly enriched in never smokers, people used to consider tobacco smoke is mutually exclusive of EGFRmut. We believed that the reason for the relatively lower EGFRmut rates in smokers was the confounding effect from the greater population of known smoke-directing lung cancers. Therefore, it remained interesting to know whether environmental tobacco smoke (ETS) exposure will influence EGFRmut rate.
a9ded1e5ce5d75814730bb4caaf49419 Method
We searched relevant studies from electronic databases. Different ETS exposure groups of non-smokers and the corresponding EGFRmut rates were extracted from eligible studies. The ETS exposure was measured by the duration (pack-years). A weighted linear regression model was used to examine the correlation by adjusting the sample size of each group.
4c3880bb027f159e801041b1021e88e8 Result
A total of 7 studies involving 1,447 patients were included. Although no difference was observed between patients with any level ETS exposure and those without any ETS exposure (OR=1.01, 0.94-1.08, P=0.787), we found a positive correlation between ETS exposure duration and occurrence of EGFRmut (R2=0.436, P<0.001; Figure 1).
8eea62084ca7e541d918e823422bd82e Conclusion
The current results suggested that tobacco smoke exposure might also be an inducing factor for EGFR mutations. The true impact of tobacco on EGFR mutations should be calculated based on general population rather than lung cancer population to avoid enrichment bias in the future studies.
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-16 - Preference of Adjuvant Treatments for EGFR-Mutant Resected NSCLC Patients: Results of a National-Wide Survey in China (ID 13390)
16:45 - 18:00 | Author(s): Jianxing He
- Abstract
Background
EGFR mutated patients represent half of NSCLC cases in China. ADJUVANT study (NCT01405079), a published multicenter RCT, showed that EGFR-TKIs were associated with significant longer DFS than chemotherapy in stage II to IIIA resected NSCLC patients. We sought to investigate the preference on adjuvant EGFR-TKI of the surgeons specializing on NSCLC in China by conducting an online national-wide survey.
a9ded1e5ce5d75814730bb4caaf49419 Method
The question ‘would you recommend EGFR-TKIs as adjuvant therapy in postoperative patients with EGFR mutation? -Yes; No’ was included on an online survey system. Interviewee personal information was also collected. Logistic regression model was conducted to explore factors associated with the choices.
4c3880bb027f159e801041b1021e88e8 Result
We received 732 responses from lung cancer surgeons from 30 provinces of China, 618 (84.43%) doctors were from department of general thoracic surgery and 114 (15.57%) surgeons from department of thoracic oncology surgery, 660 (90.16%) were from tertiary hospitals and 65 (8.88%) from the secondary ones. The interviewees consisted of 93 (12.70%) master candidates, 15 (2.05%) doctoral candidates, 98 (13.39%) residents, 217 (29.64%) attending doctors, 174 (23.77%) associate chiefs of surgeon and 135 (18.44%) chiefs of surgeon. As a result, 572 (78.1%) surgeons selected “Yes”, 143 (19.5%) selected “No”, and the rest abstained. Logistic regression analysis revealed that the result was not influenced by different career duration, location, economic status of living, hospital grade, department type, etc.
8eea62084ca7e541d918e823422bd82e Conclusion
This national-wide large sample survey showed that recommending EGFR-TKIs as adjuvant therapy for postoperative EGFR-mutant NSCLC patients was widely supported by specialists in lung cancer in China.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.11 - Screening and Early Detection (Not CME Accredited Session) (ID 977)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.11-01 - Methylation Markers That Correlate with Occult Lymph Node Metastases of NSCLC and a Preliminary Prediction Model (ID 13962)
12:00 - 13:30 | Author(s): Jianxing He
- Abstract
Background
Lymph node (LN) metastasis status is the most important prognostic factor and determines the treatment strategy. The current imaging approaches are not sufficiently precise to diagnose occult LN metastasis before surgery, while the invasive biopsy fails to be widely used. Therefore, more precise and non-invasive methods are warranted to determine the lymph node status preoperatively and lead to appropriate treatment strategy. Methylation alteration is an optimal candidate to trace the signal from early stage tumors due to its early existence, multiple loci and stability in blood. To build a diagnostic tool, we shall firstly screen and identify a set of plasma methylation markers.
a9ded1e5ce5d75814730bb4caaf49419 Method
High-throughput targeted methylation sequencing was performed on plasma and matched tissue samples from a cohort of 134 lung cancer patients with a primary lesion less than 3 cm in diameter. The methylation profiles were compared between patients with and without occult LN metastases. A preliminary prognostic model was built by random forest by integrating both top 5 hypermethylated genes and top 5 hypomethylated genes.
4c3880bb027f159e801041b1021e88e8 Result
Within this cohort, 22 cases were found to have occult LN metastases found by pathological examination. Thus, we selected the other 22 cases without occult LN metastasis by matching gender, age, smoking history and tumor histology. Hypermethylation on 32 genes, such as TNFRSF1B, DMRTA2, VAV3-AS1, HIST3H2A, PALD1, NKX2-3, MAP3K12, MAPK10, were identified between the two groups. Hypomethylation on 20 genes, such as RAB42, KCNN3, UBE2L6, RARG, CRY1, MTUS2, TMEM179, MEGF11, were also detected. 25% (13 out of 52 genes) of these markers could be found in the matched tissue samples. The AUC of ten fold cross validation of the preliminary prediction model is 0.86.
8eea62084ca7e541d918e823422bd82e Conclusion
We found some specific plasma methylation markers for occult LN metastasis of NSCLC. Further efforts should be made in establishing a non-invasive blood diagnostic tool.
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P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.16-46 - The Comparison Between Non-Intubated and Intubated Thoracoscopic Resection for Pulmonary Nodule: A Meta-Analysis (ID 13707)
12:00 - 13:30 | Author(s): Jianxing He
- Abstract
Background
General anesthesia with single-lung ventilation is considered mandatory for thoracoscopic anatomical resection for non–small cell lung cancer (NSCLC). Few studies have demonstrated non-intubated thoracoscopic surgery offers several advantages over the procedure with tracheal intubation. Thus, we performed a meta-analysis with the aim of evaluating whether non-intubated thoracoscopic anatomical resection offers better perioperative outcomes over intubated thoracoscopic anatomical resection to pulmonary nodule.
a9ded1e5ce5d75814730bb4caaf49419 Method
A comprehensive search of online databases was performed. Intraoperative and postoperative variables were compared between subgroups. The odds ratio (OR) or SMD and its 95% CI was calculated using a random effects model. Heterogeneity across studies was examined by the Cochran Q chi-square test and the I² statistic.
4c3880bb027f159e801041b1021e88e8 Result
A total of 4 eligible studies including 556 patients were recruited. All included studies had comparable baseline characteristics and surgical procedures. Non-intubated anesthesia thoracoscopic surgery was performed on 250 patients, whereas the other 306 patients underwent intubated surgery. Patients who underwent non-intubated surgery correlated with significant shorter postoperative hospital stays (SMD=-0.36, p<0.001) (Figure A) and postoperative fasting time (SMD=-2.80, p<0.001) (Figure B). Patients underwent non-intubated surgery also exhibited a trend toward lower cardiovascular complication rates (1.45% vs 2.69%, OR=0.59, p=0.551) and respiratory complication rates (8.23% vs 11.18%, OR=0.78, p=0.454), shorter anesthesia duration (SMD=-0.48, p= 0.056) and operative time (SMD=-0.07, p=0.521) with no statistical significance.
8eea62084ca7e541d918e823422bd82e Conclusion
Non-intubated thoracoscopic anatomical resection showed significantly shorter postoperative fasting time and hospital stay compared with intubated thoracoscopic anatomical resection, indicating a more rapid recovery after surgery. Further large scale study should focus on prospective validation of feasibility and safety for non-intubated thoracoscopic approach.
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