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Yuan Chen



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    JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)

    • Event: WCLC 2019
    • Type: Joint IASLC-CSCO-CAALC Session
    • Track:
    • Presentations: 1
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      JCSE01.20 - Pilot Study on the Tumor Immune Microenvironment Between Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) (ID 3434)

      07:00 - 11:15  |  Author(s): Yuan Chen

      • Abstract

      Abstract
      Background
      Tumor immune microenvironment plays an important role in immunotherapy and prognosis. However, the differences and the clinical significance between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) is still largely unknown.

      Methods
      Resected lung cancer FFPE specimens and matched peripheral blood mononuclear cells (PBMC) from six patients with NSCLC (three adenocarcinoma, three squamous cell carcinoma) and three patients with SCLC were collected. All of the nine patients underwent stage III disease. Tumor mutation burden (TMB) was evaluated by hybridization capture based next-generation sequencing with 1021 cancer associated genes. Tumor infiltrating lymphocytes (TILs) were assessed by immunohistochemistry using multiple immune markers and meanwhile the intratumoral T-cell repertoires were analyzed via high-throughput sequencing of TCR β-chain.

      Results
      Typical EGFR mutations in adenocarcinoma (2 in 3), NSCLC and RB1 mutations in SCLC (3 in 3) were observed. SCLC patients showed significantly higher TMB than NSCLC. Regarding to the tumor immune microenviroment, SCLC tumors exhibited lower infiltration of CD3+ and CD8+ TILs (P< 0.05). Furthermore, we found that SCLC patients tended to have lower TCR Shannon index (P= 0.167) and higher Clonality index (P= 0.095). Interestingly, patients with higher Shannon index exhibited better Overall Survival (OS) while Clonality was potentially associated with decreased OS. However, further study with more patients is needed to confirm the results.

      Conclusion
      Tumor immune microenvironment varies between NSCLC and SCLC patients. Specifically, less prevalent and lower diversity of TILs were observed in SCLCs. This might potentially influence survival outcomes.

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    MA01 - Oligometastatic Disease (ID 114)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Now Available
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      MA01.09 - Concomitant SBRT and EGFR-TKI Versus EGFR-TKI Alone for Oligometastatic NSCLC: A Multicenter, Randomized Phase II Study (Now Available) (ID 2214)

      10:30 - 12:00  |  Author(s): Yuan Chen

      • Abstract
      • Presentation
      • Slides

      Background

      NSCLC patients harboring EGFR mutation generally develop resistance to EGFR TKI less than one year. Prior studies indicated that local consolidative therapy is associated with improved outcomes in patient with limited metastatic NSCLC. Radiotherapy is one of the ideal control methods for locally progressed patients, however, the optimal intervention time in order to slow the occurrence of EGFR-TKI resistance for advanced NSCLC patients with EGFR-sensitive mutations is still unclear. Our preliminary clinical and animal studies suggest that early combined radiotherapy prior to EGFR-TKI resistance can significantly improve the prognosis of patients. Our hypothesis is that the optimal intervention time of radiotherapy for EGFR mutation patients is 3 months after the beginning of EGFR-TKI.

      Method

      This is a prospective, multicenter, randomized controlled study to evaluate stereotactic body radiation therapy (SBRT) as a potential treatment for limited stage IV NSCLC (primary plus up to 3 metastatic sites) with sensitive EGFR mutation. The patients did achieve partial response or stable disease after three months treatment of the first-generation EGFR-TKI would be randomized to TKI combined SBRT (TS) or TKI alone. The primary endpoint was PFS (the time from the beginning of EGFR-TKI treatment to disease progression or death). The secondary endpoint was overall survival (OS) and safety. TKI wasn’t interrupted during the irradiation.

      Result

      A total of 61 patients were enrolled from Feb, 2017 to Jan, 2019. Median follow up was 22.3 months. Patients who TS (n: 30) had a significantly longer median PFS compared to those with TKI alone (n: 31) (PFS: 17.4 vs. 8.9 months P =0.042). T790M mutation was observed in 57.9% acquired resistance patients for TS group, and 39.3% for TKI alone group. Median PFS of T790M mutated patients was 17.4 months compared to 10.3 months of TKI alone group (P = 0.007). Multivariable analysis revealed that radiation fields were positively associated with PFS, 21.8 months for just primary tumor; 10.6 months for metastatic lesions and 18.3 months for primary and metastatic lesions (P= 0.006). OS data was not yet mature. None experienced >= grade 3 SBRT related toxicities.

      Conclusion

      A trend of improved long term PFS was noted in patients receiving SBRT for primary tumor combined EGFR TKI at the third month after the beginning of TKI. Moreover, this data suggested that benefit from radiation might be associated with delay the occurrence of T790M mutation. Further studies are required to investigate the molecular mechanisms underlying this association.

      Clinical Trial information: NCT03595644

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    MA14 - The Adequate MTarget Is Still the Issue (ID 140)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA14.05 - A Randomized Phase III Trial of Fruquintinib Versus Placebo in Patients with Advanced Non-Small Cell Lung Cancer (FALUCA) (Now Available) (ID 1490)

      15:45 - 17:15  |  Author(s): Yuan Chen

      • Abstract
      • Presentation
      • Slides

      Background

      Fruquintinib, an orally active kinase inhibitor that selectively targets vascular endothelial growth factor (VEGF) receptor, demonstrated significant benefit in progression-free survival and disease control in a randomized Phase II study in patients with non-small-cell lung cancer (NSCLC) who had failed two lines of chemotherapy. This Phase III FALUCA trial is a randomized, double-blind, placebo-controlled, multicenter trial designed to confirm the efficacy in the same patient population (NCT02691299).

      Method

      From December 2015 to February 2018, 45 clinical centers across China participated in the trial. A total of 730 patients aged 18-75 with advanced NSCLC who had failed two lines of chemotherapy were screened and 527 who met the eligibility criteria were enrolled into the study. Patients were stratified based on epidermal growth factor receptor mutation status and prior use of VEGF inhibitor therapy, and were randomized in a 2:1 ratio to receive fruquintinib (n=354) or placebo (n=173) once daily in a 3 weeks on/1 week off 4-week cycle. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response. The final data cutoff was on September 21, 2018.

      Result

      Median OS was 8.94 months for fruquintinib and 10.38 months for placebo (hazard ratio, 1.02; 95% CI, 0.816 to 1.283; p=0.841). Median PFS was 3.68 months for fruquintinib comparing to 0.99 months for placebo, respectively (hazard ratio, 0.34; 95%CI, 0.279 to 0.425; p<0.001). The ORR and DCR were 13.8% and 66.7% for fruquintinib, compared with 0.6% and 24.9% for placebo (both p<0.001), respectively. The most frequent treatment-emergent adverse events with fruquintinib (≥grade 3) were hypertension (20.7%), hand-foot syndrome (11.0%), and proteinuria (1.4%). A sensitivity analysis revealed that median OS was significantly prolonged with fruquintinib compared with placebo in patients who received no subsequent systemic anti-tumor therapies (7.00 months versus 5.06 months ; hazard ratio, 0.64; 95%CI, 0.453 to 0.903; p=0.010).

      Conclusion

      The FALUCA trial failed to meet the primary end point of OS while confirming significant benefit in secondary end points including PFS, ORR and DCR. The safety profile of fruquintinib in this patient population was acceptable and consistent with that identified in the Phase II study. A post-hoc sensitivity analysis revealed that the anti-tumor therapies that patients received post disease progression probably contributed to the failure of this study on the primary end point.

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    OA02 - A New Vision of Targets and Strategies (ID 120)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      OA02.03 - The Third Generation EGFR Inhibitor (EGFR-TKI) HS-10296 in Advanced NSCLC Patients with Resistance to First Generation EGFR-TKI (Now Available) (ID 766)

      10:30 - 12:00  |  Author(s): Yuan Chen

      • Abstract
      • Presentation
      • Slides

      Background

      HS-10296 is an oral, potent, high selective third generation EGFR tyrosine-kinase inhibitor (EGFR-TKI) for sensitizing mutations, and the EGFR Thr790Met (T790M) resistance mutation which has been demonstrated by phase I study. This phase II, open-label, multicenter single-arm study was designed to confirm the efficacy and safety of HS-10296 in a large population of non-small-cell lung cancer (NSCLC) patients with EGFR T790M mutation, who had progressed after first generation EGFR-TKI treatment.

      Method

      Patients aged at least 18 years with centrally confirmed EGFR T790M-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC after first generation EGFR-TKI treatment received HS-10296 110 mg orally once daily until disease progression, or intolerable toxicity, or patient withdrawal. Patients with asymptomatic, stable brain metastases not requiring steroids were allowed to enroll. The primary endpoint was the objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1 every 6 weeks. Response endpoints (ORR and disease control rate [DCR]) were assessed in response analysis set. Secondary end points including progression-free survival (PFS), duration of response (DoR), depth of response (DepOR), overall survival (OS) and safety were evaluated in full analysis set. The final data cutoff was on Jan 5, 2019. The study is still ongoing.

      Result

      Totally, 244 patients (median age 60.8) entered study in 36 sites in mainland China (189 patients) and Taiwan (55 patients) between May 16, 2018 to Oct 23, 2018. 2 patients were excluded from the evaluable for response analysis set (n=242) due to absence of measurable disease at baseline by independent central review. At data cutoff, 182 (74.6%) patients remained on treatment. The median duration of follow-up was 4.7 months. 160 of 242 patients achieved confirmed partial responses by independent central review. The ORR was 66.1% (95% CI: 59.8-72.1). The DCR was 93.4% (95% CI: 89.5-96.2). The most common adverse reactions (≥ 10%) were blood creatine phosphokinase increased (43 [17.6%]), aspartate aminotransferase increased (29 [11.9%]), pruritus (28 [11.5%]), rash (28 [11.5%]) and alanine aminotransferase increased (26 [10.7%]). The most common all-causality grade 3 and 4 adverse events were blood creatine phosphokinase increased (14 [5.7%]) and hyponatraemia (4 [1.6%]). Serious adverse events were reported in 30 (12.3%) patients, of which 19 (7.8%) were investigator assessed as possibly treatment-related to HS-10296. Three deaths were due to adverse events; one was related to cardiopulmonary failure, other two events occurred after disease progression. There was no interstitial lung disease during study treatment.

      Conclusion

      HS-10296 has demonstrated good clinical benefit with minimal toxicity in patients with EGFR T790M-positive NSCLC patients who have progressed after first generation EGFR-TKI treatment. The Phase III study has already launched comparing HS-10296 with gefinitib in advanced NSCLC patients with EGFR sensitizing mutations. (The study was sponsored by Jiangsu Hansoh Pharmaceutical Co., Ltd.; ClinicalTrials.gov number, NCT02981108)

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-05 - What Is the Optimal Number of Examined Lymph Node in Stage IA Non-Small Cell Lung Cancer? (ID 681)

      09:45 - 18:00  |  Presenting Author(s): Yuan Chen

      • Abstract

      Background

      1.To find out the optimal number of examined lymph nodes (ELNs) in stage IA non-small cell lung cancer (NSCLC). 2.To figure out whether there was a turning point beyond which ELNs might have adverse effects on survival.

      Method

      Using the Surveillance, Epidemiology, and End Results registry (SEER) database, we selected all NSCLC patients diagnosed with stage IA (T1N0M0) from 1995 to 2015. Cases from 1995 to 2005 were as analytical data set (group 1) and those from 2006-2015 as validation data set (group 2).The overall survival (OS) of patients with different ELNs was compared statistically by SPSS. The optimal cut point of ELNs was calculated by X-Tile and verified by univariable and multivariable analyses. Propensity score matching (PSM) was done by R software 3.5.2.

      Result

      In total, we extracted 57481 stage IA NSCLC patients (group 1, n = 20814; group 2, n = 36667). The PSM of Group 1 and Group 2 were balanced based on sex, age and race. In both groups, we divided patients into 3 subgroups, recorded as ELN = 0, 1≤ ELNs < n and ELNs≥ n. ELN = 0 had the highest risk of death in each subgroup (all p < 0.001). From n = 6 to n = 16, OS was significantly different between 1 ≤ ELNs < n, and ELNs ≥ n. But from n = 17 to n = 30, OS was the same between 1 ≤ ELNs < n and ELNs ≥ n. When dividing patients into ELNs = 0, 1-2, 3-5, 6-9, 10-29, ≥ 30,serial improvement in OS was seen with increasing ELNs, up to ELNs = 6-9, and beyond which there was little further incremental survival benefit. The survival curve of ELNs ≥ 30 even had an obvious trend to drop down.

      Conclusion

      For stage IA NSCLC, we suggested resecting 6-9 LNs was enough, and no more than 16 LNs. More than 16 ELNs did not improve survival and more than 30 ELNs might have a detrimental effect on survival.

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    P2.11 - Screening and Early Detection (ID 178)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.11-44 - A Preliminary Study Investigating the Impact of Platelet on Circulating Tumor Cell Enumeration (Now Available) (ID 1190)

      10:15 - 18:15  |  Presenting Author(s): Yuan Chen

      • Abstract
      • Slides

      Background

      Circulating tumor cell (CTC) is generally considered as the source of cancer metastasis. Blood platelet has been reported to interact with CTCs and enhance its survival. However, the masking effect of blood platelet may lead to the false-negative results in CTC test. In this preliminary study, we aimed to investigate the impact of platelet on CTC enumeration.

      Method

      A total of 73 treatment-naïve participants with indeterminate pulmonary nodules according to computed tomography scan were recruited. Three milliliters of baseline peripheral blood samples were collected from each participant for CTC enumeration. Negative enrichment and ligand-targeted polymerase chain reaction methods were used to examine the expression level of folate receptor-positive CTC (FR+CTC). All participants subsequently undergo surgery or biopsy to obtain tumor specimens for pathological assessment. ROC analysis was used to determine the diagnostic performance of FR+CTC. For the recruited lung cancer patients, the association between FR+CTC levels and platelet count was also analyzed..

      Result

      figure1.jpg47 patients with pathologically confirmed lung cancer and 26 patients with benign lung diseases (considered as the control group) were included in this analysis. In agreement with previous studies, lung cancer patients showed a significantly higher FR+CTC level compared to the control group (10.6 versus 7.7 FU/3 mL, P<0.0001). With 9.1 FU/3 mL as the cut-off threshold, the sensitivity and specificity of FR+CTC were 87.23% and 76.92%, respectively (Area under curve=0.9006, 95% confidence interval: 0.8291-0.9720). Among the 42 patients with platelet count in the lung cancer group, 36 (85.7%) were positive for CTC and 6 (14.3%) were negative for CTC. The levels of platelet count in CTC-positive group were lower than those in CTC-negative group, but the difference was not statistically significant (217.8±73.6 versus 253.5±41.4 ×109 /L, P=0.1833). Correlation was also not statistically significant between the FR+CTC level and platelet count (Spearman R=-0.2113, P=0.0993).

      Conclusion

      CTC enumeration in this study was not affected by the surface epitope masking effect of blood platelet, suggesting that FR+CTC detection has better applicability than the positive enrichment and immunocytochemical method. Further systematic study is required to validate the hypothesis.

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