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Sylvestre le Moulec



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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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      MA08.09 - Impact of Brain Metastases in Immune Checkpoint Inhibitors (ICI) Treated Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 12575)

      16:10 - 16:15  |  Author(s): Sylvestre le Moulec

      • Abstract
      • Presentation
      • Slides

      Background

      Brain metastases (BM) are frequent in NSCLC. Unfortunately, patients with (untreated) BM are often excluded from ICI trials so that their outcome on ICI is largely unknown..

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective data collection of all consecutive advanced ICI treated NSCLC patients in 6 centers (5 French, 1 Dutch) (nov 2012 – march 2018). Active BM was defined as non-irradiated new and/or growing lesions on brain imaging < 6 weeks before ICI start. Progression free survival (PFS), overall survival (OS) and site of progression on ICI was collected.

      4c3880bb027f159e801041b1021e88e8 Result

      945 patients included: 63% male, 83% WHO PS 0-1, median age 64 years, 73% non-squamous, 4% targetable driver mutations, 33% known PD-L1 (65% ≥1% expression). ICI treatment was median 2nd line (range 1-12), 94% had monotherapy PD-(L)1 inhibition. 241 patients (26%) had BM, 68% had previous cranial irradiation, 40% had active BM. BM patients were significantly younger than others (61 vs 66 years), had more adenocarcinoma (78 vs 62%), more organs involved (median 3 vs 2), a poorer PS (0-1: 76 vs 85%) and more steroids at baseline (26 vs 9%). Median follow-up: 15 months. Median (95% CI) PFS and OS without and with BM were 2 (2-3) vs 2 (1-2) months and 13 (9-16) vs 9 (7-13) months, respectively. In multivariate analysis, > 2 metastatic sites, PS ≥2 and steroids use were associated with worse PFS and OS, BM were not (table 1). In univariate analysis of BM patients, active BM were not associated with worse outcome compared to stable BM (HR PFS 0.98 (p=0.66), HR OS 0.93 (p=0.92)). Progressing BM patients had more often brain PD and a dissociated response (not specifically brain dissociated) on ICI (40 vs 12% and 13 vs 7%, respectively).

      Factor PFS HR (95% CI) p-value OS HR (95% CI) p-value
      Age > 65 vs ≤ 65 1.02 (0.87-1.20) 0.79 1.11 (0.92-1.34) 0.29
      Smoking yes vs no 0.53 (0.41-0.69) <0.001 0.81 (0.59-1.12) 0.20
      Histology squamous vs adeno 1.07 (0.89-1.28) 0.78 1.24 (0.99-1.55) 0.12
      Nr of organs with metastases > 2 vs ≤ 2 1.28 (1.09-1.50) 0.003 1.48 (1.22-1.80) <0.001
      Immuno line > 2 vs ≤ 2 1.11 (0.94-1.30) 0.22 1.10 (0.91-1.33) 0.34
      WHO PS 0-1 vs ≥2 2.14 (1.75-2.62) <0.001 3.48 (2.78-4.36) <0.001
      Use of corticosteroids yes vs no 1.36 (1.10-1.69) 0.005 1.31 (1.03-1.68) 0.03
      BM yes vs no 1.05 (0.88-1.26) 0.58 0.96 (0.77-1.19) 0.70

      8eea62084ca7e541d918e823422bd82e Conclusion

      BM, treated or active, do not negatively impact outcome on ICI although BM failure is more common in these patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-09 - Efficacy and Tolerance of Osimertinib in Real Word Setting: Results of the French Early Access Program (EXPLORE T790M GFPC Study). (ID 11335)

      16:45 - 18:00  |  Author(s): Sylvestre le Moulec

      • Abstract
      • Slides

      Background

      Based on the Phase III AURA3 trial, osimertinib a third-generation EGFR TKI is approved in France in EGFR T790M-positive advanced NSCLC whose disease have progressed on or after first or second generation EGFR TKI.

      Objective: to assess efficacy and tolerance of Osimertinib in real world setting.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective, multicentric study including T790M-positive advanced NSCLC receiving osimertinib from 07 April 2015 to 27 April 2016 in French early access program. Overall survival (OS) and progression free survival PFS) were analyzed in the whole population, in the subgroup of patients with cerebral metastasis at osimertinib initiation and according to the number of previous treatment lines (1 versus 2 or more).

      4c3880bb027f159e801041b1021e88e8 Result

      The analysis included 205 patients treated in 52 centers; mean age 69.5 ± 11.1 years, female 68.8%, adenocarcinoma 97.5%, EGFR mutations exons 19/21: 66.5%/ 30.5%, never smokers 71.5 %, PS 0-1/2/ 3-4: 54%/18,8%/27.2%, stage IV: 87.4%,presence of cerebral metastasis at osimertinib initiation: 43.7% .

      EGFR T790M mutation diagnosis have been done by liquid biopsy in 34.4 % or on tissue re-biopsy in 65.6%. Patients received a median of 2.8 ± 1.5 lines of treatment before osimertinib initiation. All patients received a first or second generation EGFR TKI before osimertinib. Osimertinib has been used in second line setting in 18% of cases and in third line or more setting in 82%.

      Median PFS was 12.4 (CI 95%: 10.1-15.1) months in the whole population, 9.7 (CI 95%: 7.7-13.5) in patients with cerebral metastasis and 15.8 (CI 95%: 11.9-17) months in patients without cerebral metastasis, (p : 0.2). PFS was not significantly different according to the use of osimertinib as second or third line of treatment: 12.6 (CI 95%: 6.7-17.5) vs 12.4 (CI 95%: 9.7-15.3) months, respectively.

      Median OS since osimertinib initiation was 20.5 (CI 95%: 16.9-24.3) months, 23.06 [18.56;27.83] and 18.00 [12.16;22.21] months in patients without and with cerebral metastasis, respectively. OS was not significantly different according the use of osimertinib as second or third line of treatment: 17.5 (CI 95%: 11.6;27.8) vs 21.7 (CI 95%: 17.3;24.3) months (p=0.4).

      A new biopsy was performed at disease progression on osimertinib in 50 patients: data will be presented.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Efficacy of Osimertinib in real world setting appears similar to that observed in clinical trials in patients with EGFR T790M mutation in ≥2ndline.

      Clinical trial information: Supported by an academic grant from Astra Zeneca

      6f8b794f3246b0c1e1780bb4d4d5dc53

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