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P. Martin



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    MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI05.13 - Treatment of EGFR/ALK-Driven Non-Small Cell Lung Cancer (NSCLC) Brain Metastases: Impact of First-Line Whole Brain Radiotherapy on Outcome (ID 1251)

      17:55 - 18:00  |  Author(s): P. Martin

      • Abstract
      • Presentation
      • Slides

      Background:
      Brain metastases (mets) in EGFR/ALK-driven NSCLC are common, and frequently pose treatment dilemmas. Effective systemic therapy with tyrosine kinase inhibitors (TKIs) controls extracranial disease in up to 70% of patients, but often radiotherapy is required for intracranial control. As whole brain radiation (WBRT) may be associated with neurocognitive toxicity, we aimed to evaluate the impact of molecularly targeted therapy and stereotactic radiotherapy (SRS) for EGFR/ALK-driven NSCLC on intracranial disease control with and without WBRT.

      Methods:
      This retrospective analysis included patients treated with EGFR/ALK-positive NSCLC at Princess Margaret Cancer Centre from 1998-2015, with brain mets at lung cancer diagnosis or during treatment/follow-up. Demographic data were collected from electronic patient records. Time to intracranial progression (TTIP) and overall survival (OS) were calculated from date of diagnosis of brain mets, using the cumulative incidence function and Kaplan-Meier methods respectively; differences between groups were tested with Gray’s or log-rank test.

      Results:
      From 1998-2015, 162 patients with brain mets from EGFR/ALK-driven NSCLC were identified: 138 in the EGFR cohort, 23 in the ALK cohort and one included in both cohorts for analysis, whose tumour carries both an EGFR mutation and ALK rearrangement. Table 1 contains clinical characteristics and treatment details. In the EGFR cohort, initial brain mets treatment consisted of systemic therapy alone in 19 patients (17 TKI, 2 chemotherapy), SRS +/- surgery in 27 patients and WBRT +/- SRS/surgery in 88 patients. 1-year intracranial progression rates were 26%, 32% and 12%, respectively, and median TTIP was 18, 16 and 40 months [p=0.12]. Median OS was 26, 27 and 34 months respectively [p=0.49]. In the ALK cohort, initial brain mets treatment consisted of systemic therapy alone in 4 patients (1 TKI, 3 chemotherapy), SRS/surgery alone for 4 patients and WBRT +/- SRS/surgery for 15 patients. 1-year intracranial progression rates were 50%, 50% and 13%, respectively, and median TTIP was 18, 14 and 69 months [p=0.028]. Median OS was 35 months, not reached and 51 months, respectively [p=0.75]. Multivariable analysis for the whole group showed that age [p=0.021], number of brain mets [p=0.012] and extracranial control [p=0.008] were significantly associated with OS, but not WBRT [p=0.61].

      Conclusion:
      In this cohort of patients with brain mets from EGFR/ALK-driven NSCLC, patients treated with WBRT trended to longer TTIP. Although not statistically significant, our data also show a trend towards longer survival in patients who received WBRT. These observations require further validation in this patient population.

      EGFR (N=139) ALK (N=24)
      Median Age (Range) 59(29-86) 53(31-77)
      Female Sex 93(67%) 15(62%)
      Ethnicity Asian Caucasian Other 58(42%) 63(45%) 18(13%) 7(29%) 13(54%) 4(17%)
      Smoking Never Smoker Former/Current Smoker Unknown 108(77%) 30(22%) 1(1%) 19(79%) 5(21%) 0
      ECOG PS (Diagnosis) 0 1 2-4 66(48%) 67(48%) 6(4%) 7(29%) 14(58%) 3(13%)
      Brain Mets at Stage IV diagnosis 93(67%) 13(52%)
      Number of Brain Mets 1 2-4 5+ N/A 32(23%) 39(28%) 62(45%) 6(4%) 9(38%) 6(24%) 9(38%) 0
      Symptomatic Brain Mets No Yes 78(56%) 61(44%) 16(67%) 8(33%)
      Initial Brain Mets treatment WBRT WBRT+SRS/Surgery SRS+/-Surgery Systemic Therapy None 71(51%) 17(12%) 27(19%) 19(14%) 5(4%) 13(54%) 3(12%) 4(17%) 4(17%) 0


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