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Zhaoxia Wang



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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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      P1.01-105 - Lung Cancer Patients with Concurrent EGFR and MET Mutations: A Retrospective Analysis of 29 Cases (ID 12864)

      16:45 - 18:00  |  Presenting Author(s): Zhaoxia Wang

      • Abstract
      • Slides

      Background

      It has been reported that about 5%-20% of EGFR-TKIs resistant NSCLC patients harbors MET amplification or activating mutations. However, the extent that MET abnormal activation contributes to EGFR-TKIs resistance remains widely unknown. Here, we describe the clinical and genetic characteristics of 29 lung cancer patients harboring concurrent EGFR and MET mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Genetic mutations were reviewed in 6000 lung cancer patients who underwent genetic testing at our institute from 2016 to 2018. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes).

      4c3880bb027f159e801041b1021e88e8 Result

      The selected patients included 24 lung adenocarcinoma patients, 1 squamous cell lung cancer patient and 3 lung cancer patients with unspecified pathology. Both MET amplification and activating mutations were included for analysis. MET amplification was detected in 90% (27/30) of samples, while activating mutations was present in 13.3% (4/30) of samples, including H1112Y, D1228N, D1246Y and D1246H. 14% (4/29) of patients had not received EGFR-TKIs treatment before genetic testing, which were considered as primary resistance. 79% (23/29) of patients were treated with EGFR-TKIs. Surprisingly, 60% (18/30) of cases had other functional mutations which may also affect the effectiveness of EGFR-TKIs, such as EGFR T790M mutation (3 cases), rare EGFR mutations (I744M, R108K and C769S, 3 cases), EGFR amplification (7 cases), CDK4 amplification (2 cases), loss-of-function mutations of CDKN2A (2 cases) and so on. One patient had two samples tested. He was resistant to gefitinib and osimertinib, and EGFR L858R mutation and MET amplification were detected in the first sample. Later, he was treated with combined gefitinib and crizotinib and reached PR at the 2nd month. However, his disease finally progressed probably due to an additional MET mutation (D1246Y) that caused resistance to crizotinib.

      8eea62084ca7e541d918e823422bd82e Conclusion

      MET amplification and activating mutations may lead to primary and acquired resistance of EGFR-TKIs. Moreover, additional potentially resistant mechanisms were detected in most cases. Therefore, it is apparently requisite to provide a comprehensive genetic testing to lung cancer patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.01-90 - A Pilot Trial Assessing Apatinib Combined with Docetaxel (DTX) as Second-Line Chemotherapy for EGFR Negative Advanced NSCLC) (ID 13105)

      16:45 - 18:00  |  Author(s): Zhaoxia Wang

      • Abstract
      • Slides

      Background

      Apatinib is a new tyrosine kinase inhibitor against vascular endothelial growth factor receptor 2 and improves outcomes in patients (pts) with metastatic gastric cancer as a third line of treatment. Recently, it has been reported effective as third- or later-line treatment in advanced NSCLC. This prospective study tried to assess the efficacy and safety of apatinib combined with DTX as second-line treatment of EGFR negative NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this open-label single-arm study, pts recived oral apatinib (500mg, p.o. qd) with DTX(60mg/m2,i.v. d1 q3w) as second-line therapy. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the RECIST 1.1. Treatment was continued until disease progression, death, or intolerable toxicity.

      4c3880bb027f159e801041b1021e88e8 Result

      Between September 2016 and April 2018, 27 pts were enrolled. In 27 pts, there were 23 pts available for efficiency evaluation and 27 pts available for safety evaluation. In the first evaluation of efficacy at one month, computed tomography scan evaluation revealed that partial response (PR) occurred in 7 of 23 pts and other 15 showed stable disease (SD). The median PFS was 4.0667 months (95% CI: 2.5333–6.3333 months). The median OS was 10.5667 months (95% CI: 10.5667– ~ months). The objective response rate(ORR) was 30.43% and disease control rate(DCR) was as high as 95.65 %. Most of the adverse reactions (AEs) were at grade 1 or 2. The grade 3 AEs were hypertension (n=12, 44.44%), hand-foot syndrome (n=3, 11.11%), diarrhea (n=2, 7.41%), mouth ulceration (n=3, 11.11%), thrombocytopenia (n=1, 3.70%). No grade 4 AE or drug-related mortality occurred.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Apatinib has a potential application prospect in second-line therapy combined with DTX for EGFR negative NSCLC pts. The research team will continue the study.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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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: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-102 - Comprehensive Next-Generation Sequencing Guided Targeted Therapies Improve Clinical Outcomes of Lung Cancer Patients (ID 13445)

      16:45 - 18:00  |  Presenting Author(s): Zhaoxia Wang

      • Abstract
      • Slides

      Background

      Next-generation sequencing (NGS) has been increasingly involved in the clinical decision-making of cancer care, the primary applications of which are the identification of sensitizing mutations for targeted therapies and drug-resistant mechanisms. Along with more clinical validations and approvals of several commercially available targeted NGS panels by FDA for mutation profiling, it has been debated that whether comprehensive NGS test should be used as a standard procedure in clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this study, we recruited 24 patients with stage IV lung cancer. 22 of them are adenocarcinoma and the other 2 are small cell lung cancer and squamous cell carcinoma, respectively. Genomic DNA from 13 tumor tissues, and circulating tumor DNA from 8 pleural effusions and 3 plasma samples in each corresponding patient were collected and subjected to targeted-NGS covering 416 cancer-related genes and 16 genes frequently rearranged in solid tumors. Targeted therapy or chemo/radiochemotherapy was applied in clinical practice with the consideration of patients’ requests and their affordability due to financial barriers. Patients’ clinical outcomes were further evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      Of all patients, 54% of them (n=13) were detected with sensitizing mutations that have targeted drugs available, including EGFR exon 19 deletion (n=2), L858R (n=2) and L861Q mutations (n=1), ALK fusion (n=1), ROS1 fusion (n=1), MET exon 14 skipping (n=1), as well as EGFR T790M (n=5) for 4 patients who had progressed on the first-generation tyrosine kinase inhibitors (1st-gen TKI) and 1 TKI-treatment naive patient. 69% of patients (n=9) with actionable mutations were subjected to targeted treatment, while the other 31% patients (n = 4) were treated with chemotherapy or radiochemotherapy. Consistent with clinical validations, the overall survival (OS) of targeted-treatment group is better than the systematic treatment group. On the other hand, for patients without detectable actionable mutations (n=11), 64% of patients (n=7) were underwent chemotherapy, while the rest were treated with 1st-gen EGFR TKI as requested by the patients. As expected, chemotherapy-treatment group had a similar OS as the TKI group. Collectively, patients with sensitizing mutations achieved significantly longer OS from the TKI treatments than those without actionable mutations (p=0.02).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data demonstrated that the existence of sensitizing mutation is the determining factor for the treatment efficacy of targeted therapies. In the real world, NGS test can not only be involved into the decision-making for the first line treatment, but also be instructive for treatment changes after drug-resistance developed

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • 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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      P3.01-106 - Real-World Data to Evaluate the Clinical Benefit of NGS for Directing Lung Adenocarcinoma Treatment (ID 12870)

      12:00 - 13:30  |  Presenting Author(s): Zhaoxia Wang

      • Abstract
      • Slides

      Background

      Since mid-2017, multiple NGS-based companion diagnostic tests have been approved in NSCLC to select patients eligible for targeted therapy and immunotherapy. Here, we retrospectively analyzed the benefit of NGS for advanced lung adenocarcinoma in routine clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From 2016 to 2018, the samples taken from 9 lung adenocarcinoma patients were sent to Geneplus-Beijing Institute for genetic testing. Mutation profiles were analyzed using hybridization capture based NGS, which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes). The tumor response was evaluated using RECIST v1.1.

      4c3880bb027f159e801041b1021e88e8 Result

      Six tumor tissue samples, two blood samples and one pleural effusion sample were analyzed (Table 1). No actionable mutation was detected in patient 1 and then he left hospital without additional treatment. The KRAS mutation present in patient 2 suggested that he might be resistant to EGFR-TKIs. Therefore, he received chemotherapy. According to the genetic testing results, all the other patients received EGFR-TKIs and the disease control rate was 100% at the 2nd month. Apart from EGFR T790M mutation, EGFR amplification was present in patient 8 with disease progression following gefitinib therapy. She received osimertinib and achieved PR at the 2nd month. The response has maintained for over 7 months up to now, which made us reconsidering the controversial correlation between EGFR amplification and EGFR-TKI effectiveness. Rare EGFR mutation and MET amplification were detected in patient 9, and then he was treated with icotinib.The best response was SD at the 4th month. However, he died of pulmonary embolism or cerebral infarction, making the duration of response 4 months.

      Table 1. Clinical and genetic characteristics of 9 patients   
      Patient No Age/Gender Sample Previous Targeted Therapy Actionable Mutations Following Treatment Response Evaluation (2nd month) Duration of response (months)
      1 72/Male Blood No No No treatment Not applicable Not applicable
      2 62/Male Tissue No KRAS p.G12A, STK11 p.D53Gfs*110 Chemotherapy Not available Not available
      3 62/Male Tissue No EGFR p.L747_T751del (EX19del) Gefitinib PR 20+
      4 63/Female Tissue No EGFR p.L858R (EX21) Gefitinib PR 5+
      5 75/Female Tissue No EGFR p.L858R (EX21) Icotinib SD 11+
      6 63/Male Blood Icotinib EGFR p.L858R (EX21),CHEK2 c.445-1G>A Combined gefitinib and bevacizumab SD 6+
      7 79/Male Tissue No EGFR p.L747_T751del (EX19), NF1 c.587-1G>C, ATM c.2124+1G>T Gefitinib PR 2+
      8 80/Female Pleural effusion Gefitinib EGFR p.L858R (EX21), EGFR p.T790M (EX20), EGFR amplification Osimertinib PR 7+
      9 81/Male Tissue No EGFR p.G719A (EX18), MET amplification, CDK4 amplification Icotinib SD 4
      8eea62084ca7e541d918e823422bd82e Conclusion

      NGS-based genetic testing comprehensively predicts the effectiveness of targeted therapy. It can be widely used in routine clinical practice.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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