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Qian Chu



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    OA07 - Oligometastasis: What Should Be the State-Of-The-Art? (ID 905)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 107
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      OA07.03 - Addition of Local Therapy to EGFR TKI Showed Survival Benefit in EGFR-Mutant NSCLC pts with Oligometastatic or Oligoprogressive Liver Metastases (ID 12263)

      15:35 - 15:45  |  Author(s): Qian Chu

      • Abstract
      • Presentation
      • Slides

      Background

      Our previous study demonstrated that EGFR-mutant NSCLC patients (Pts) with liver metastases (LM) showed poor response to EGFR-TKIs than those without LM, suggesting that additional treatment is warranted. Recently, several clinical studies indicated that local therapy (e.g. surgery and radiotherapy) could significantly improve progression-free survival (PFS) in NSCLC Pts with oligometastatic or oligoprogressive disease. This study aimed to investigate whether addition of local therapy to EGFR-TKIs could provide a better survival benefit than TKIs alone in EGFR-mutant NSCLC Pts with oligometastatic or oligoprogressive LM.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Pts with EGFR-mutant NSCLC and LM were enrolled. Oligometastatic LM was defined as < 5 sites in liver without extrahepatic metastases at initial diagnosis. Oligoprogressive LM was defined as < 5 sites in liver without extrahepatic metastases during TKIs therapy. For oligoprogressive cohort, PFS1 was calculated from time of initiation of TKI therapy to first RECIST 1.1 defined progress disease (PD) or death. PFS2 was calculated from time of initiation of TKI therapy to off-TKI PD.

      4c3880bb027f159e801041b1021e88e8 Result

      Totally, 135 cases with EGFR-mutant NSCLC and LM were eligible (64 with oligometastatic LM and 71 with oligoprogressive LM). In oligometastatic cohort, 20 Pts received EGFR-TKIs (E) and 23 Pts received EGFR-TKIs plus local therapy (E+LT) as first-line treatment. The addition of local therapy showed a significantly longer PFS (12.9 vs. 7.9 m, P = 0.041) and OS (36.8 vs. 21.3 m, P = 0.034) than EGFR-TKIs alone. In oligoprogressive cohort, 24 Pts received continuation of EGFR-TKIs plus local therapy (cE+LT) and 25 Pts received switch therapy (ST). Median PFS1 was similar. Median PFS2 (13.9 vs. 9.2 m, P = 0.007) and OS (28.3 vs. 17.1 m, P = 0.011) was significantly longer in cE+LT group than in ST group. Multivariate analysis revealed that addition of local therapy was independently associated with prolonged PFS (HR = 0.435, P = 0.028) and OS (HR = 0.434, P = 0.071) in Pts with oligometastatic LM. Distant metastatic sites were the major pattern of failure in EGFR-TKI plus local therapy group while locoregional recurrence including primary lesions and LM was the major reason in TKI alone group.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The current study suggested that EGFR-TKIs plus local therapy demonstrated the prolonged survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC Pts with oligometastatic or oligoprogressive LM. These findings suggest that local therapy should be further explored in large-scale, strictly designed clinical trials as a standard treatment option in this clinical scenario.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • 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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      P3.13-12 - A Lung Adenocarcinoma with Concomitant EGFR and de novo MET Amplification Response Well to Combination of TKI and Bevacizumab (ID 13975)

      12:00 - 13:30  |  Presenting Author(s): Qian Chu

      • Abstract
      • Slides

      Background

      Patients with NSCLC who are carrying concomitant de novo EGFR and MET amplification were commonly reported to have poor response to therapy. Here, we presented a case of a patient harboring concomitant de novo MET and EGFR, who obtained favorable response to combinatorial therapy of TKI and bevacizumab.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We presented a lung adenocarcinoma patient harboring dual EGFR-MET alterations, and evaluated his response to combinatorial therapy of TKI and bevacizumab. In vitro experiments were performed in HCC827(EGFR-19del) and HCC827-GR (EGFR-19del+MET amplification) cells to validate the effect of bevacizumab on MET pathway.

      4c3880bb027f159e801041b1021e88e8 Result

      A 44-year-old male stage IV lung adenocarcinoma with left lung tumor was detected harboring of EGFR-19del and MET amplification using PCR and FISH. The patient was treated with erlotinib+bevacizumab and achieved partial response (PR) with a PFS with 13 months. After PD, NGS performed on both tissue and plasma biopsies revealed that the patients obtained first-generation resistant mutation EGFR-T790M, concomitant with EGFR-19del. The patient was treated with osimertinib+bevacizumab and achieved PR. He developed PD again with a PFS of 10.2 months, and repeated biopsies sequencing identified concomitant EGFR-19del and MET amplification. Then, the patient was treated with crizotinib+bevacizumab and the best curative effect was stable disease. Four months later, he developed PD and the third biopsy still revealed positive EGFR-19del and MET amplification. The patient received osimertinib+crizotinib+bevacizumab and he achieved PR one month after treatment initiation. He is still under the treatment and the PFS is more than eight months. In vitro data revealed that, under gefitinib treatment, cell viability was higher in HCC827(EGFR-19del) than HCC827-GR (EGFR-19del+METamp). However, the patient harboring dual EGFR-MET alterations in this study obtained a PFS of 13 months to erlotinib, similar with patients with EGFR-19del only (mPFS was 13 months to erlotinib as reported), suggesting the efficacious treatment of EGFR-TKI and bevacizumab than TKI alone. We observed that VEGFR-2 was expressed at relatively high levels in HCC827-GR than other cell line without METamp, and VEGF pathway inhibition by bevacizumab resulted in decreased phospho-c-Met in HCC827-GR cell lines. This result provided in vitro evidence that bevacizumab can reduce MET pathway activation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study provided basic knowledge and evidence for patients harboring concomitant EGFR and de novo MET amplification who may obtain favorable response to combinatorial treatment of TKI and bevacizumab. Encouraging antitumor activity of TKI+bevacizumab support further development of this combination for patients with advanced NSCLC and other solid tumors.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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