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Oscar S.H. Chan



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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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      OA07.02 - ATOM: A Phase II Study to Assess Efficacy of Preemptive Local Ablative Therapy to Residual Oligometastases After EGFR TKI (ID 12977)

      15:25 - 15:35  |  Presenting Author(s): Oscar S.H. Chan

      • Abstract
      • Presentation
      • Slides

      Background

      NSCLC patients (Pts) harboring EGFR mutation invariably develop resistance to EGFR TKI at a median time of 9-13 months. Prior studies have showed that local ablative therapy (LAT) upon oligoprogression (OP) can extend the duration of TKI therapy effectively. We postulate that residual positron emission tomography (PET) avid lesions after initial treatment of EGFR TKI may harbor resistant clones and preemptive LAT may improve progression free survival (PFS).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This single-arm phase II study aims to determine the efficacy of preemptive LAT to residual metabolic active oligo-metastases after initial TKI. Pts with stage IIIB/ IV EGFR M+ NSCLC who possessed oligoresidual (OR) disease (≤ 4 PET-avid lesions with SUV ≥2.5) after a 3-mth TKI therapy were enrolled. Those with initial PR underwent screening PET-CT. PET avid ORs would be treated by LAT, either by stereotactic ablative radiotherapy (SABR) or surgery per clinicians’ discretion. TKI was continued after LAT until it was considered ineffective. PET-CT was done on the 3rd and 12th month post-LAT (or at progression), apart from regular imaging. Further LAT was allowed if OP was detected. Primary endpoint was PFS rate at 1 year from enrollment. Overall survival (OS), treatment safety and comparison with screen failure cohorts were secondary endpoints.

      4c3880bb027f159e801041b1021e88e8 Result

      18 Pts were enrolled from 2014-17. Recruitment was stopped before the planned number (n = 34) due to slow accrual. Two were not analyzed due to consent withdrawal and significant protocol violation. Median follow up was 28.7 mth. Among the 16 analyzed Pts, the 1 year PFS rate (i.e. 15 mth post TKI) was 62.5%. OS data was not yet mature. All LAT were done by SABR, and none experienced ≥grade 3 SABR related toxicities. Compared with screen failure cohort (n = 43, metabolic CR or PR with residual disease not fulfilling LAT criteria), the 1 year and 2 year PFS favored treatment arm, though statistically not significant (62.5% vs 47.1%, 30.0% vs 7.9%; p = 0.15).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The 1-yr PFS rate is encouraging. A trend of improved long term PFS is noted in Pts receiving preemptive LAT to residual PET-avid OM after initial TKI compared with Pts without LAT. Further studies are warranted.

      Clinical Trial information: NCT01941654

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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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      P2.01-53 - Local Treatment for Oligoprogression/Oligometastases After Failure to Crizotinib for ALK-Rearranged Stage IV Lung Cancer (ID 12044)

      16:45 - 18:00  |  Author(s): Oscar S.H. Chan

      • Abstract
      • Slides

      Background

      Crizotinib is approved as 1st line treatment for ALK-rearranged stage IV non-small-cell lung cancer (NSCLC). We investigated if local treatment for oligoprogression/metastases (<=5 lesions) while maintaining crizotinib could prolong progression-free survival (PFS) for ALK-rearranged stage IV NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a retrospective review on crizotinib for ALK-rearranged stage IV NSCLC in the real-world setting in 4 public oncology hospitals. All patients who received crizotinib outside clinical trials were reviewed. Patients who developed oligoprogression/metastases following progressive disease to crizotinib were assessed for local treatment (surgery, palliative or radical radiotherapy or combination of surgery and radiotherapy) for these sites while continuing crizotinib until further progressive disease beyond the definition of oligoprogression/metastases. The primary study endpoint is PFS after local treatment for olioprogression/metastases. Secondary endpoints are overall survival and toxicity profiles.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 165 patients were recruited, of which 115 (69.7%) and 50 (30.3%) received it as 1st line treatment and at later lines respectively. Of the 161 (97.6%) patients eligible for tumour response assessment, the objective response rate was 64.5%. After a median follow up of 18.5 months (range 0.6-70.1 months), the median PFS and OS of the whole population were 10.8 and 18.5 months. There was no statistical difference in PFS and OS among those who received crizotinib as 1st line and later lines. Twenty-nine (17.6%) patients developed oligoprogression/oligometastasis following crizotinib. Eighteen (62.1%) received local treatment (surgery – 2 , stereotactic radiosurgery/radiotherapy – 7, intensity-modulated radiation therapy/tomotherapy – 3, palliative radiotherapy – 7), of whom 3 patients received 2 courses of local treatment to different oligoprogressive/oligometastatic sites at oncologists’ discretion while continuing crizotinib until their next date of progressive disease. Median PFS was significantly longer in those who received local treatment (20.9 months [95% CI 11.8-30.1 months] vs. 11.4 months [95% CI 5.1-17.7 months]; p=0.004) than those who did not for their oligoprogression/oligometastases. Median OS was not different between those who received local treatment and those who did not for their oligoprogression/oligometastases (p=0.742). Seventy-one (43.0%) patients received other ALK inhibitors following progression to crizotinib (1 line – 50, 2 lines – 19, 3 lines – 1, and 4 lines – 1). Four (2.4%) patients are still receiving crizotinib without progression. Crizotinib was well-tolerated with only 7.9% grade 3/4 adverse events. No grade >=2 events were reported for local treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Local treatment for oligoprogressive/metastatic diseases could significantly prolong PFS in the real-world setting, which procrastinates the later use of other systemic therapies.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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