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N.B. Kumarakulasinghe



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    P1.11 - Poster Session/ Palliative and Supportive Care (ID 229)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Palliative and Supportive Care
    • Presentations: 1
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      P1.11-002 - The Impact of Gastric Acid Suppressive Therapy on Treatment Outcomes of EGFR Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer (ID 804)

      09:30 - 17:00  |  Author(s): N.B. Kumarakulasinghe

      • Abstract
      • Slides

      Background:
      Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors such as gefitinib and erlotinib are dependent on gastric pH for absorption which may be affected by concomitant gastric acid suppressive therapy (AS) with proton pump inhibitors and histamine 2 antagonists. We sought to determine the effect of gastric acid suppressive therapy on overall survival (OS) in patients treated with EGFR tyrosine kinase inhibitors.

      Methods:
      Patients with advanced stage non-small cell lung cancer harboring EGFR mutations treated with EGFR tyrosine kinase inhibitors were retrospectively identified. Medical records in our single institution were reviewed from 1[st] January 2008 to 30[th] December 2013. Patient clinico-pathological characteristics,use of gastric acid suppressive therapy and the overall survival were obtained. Statistical analysis was performed using chi[2], log rank test and cox regression where indicated

      Results:
      We identified 191 patients. The median age of patients was 64 years (range: 30-89) ,109 (57.1%) were female, 117(61.3%) were never smokers, 91 (47.6%) harbored EGFR exon 19 deletion and 144 (75.4%) received EGFR tyrosine kinase inhibitors as first line treatment. 55 (28.8%) patients received gastric acid suppressive therapy The groups of patients who received gastric acid suppressive therapy and those who did not receive gastric acid suppressive therapy were similar with regards to gender, smoking status, and type of EGFR mutations, Charlson co-morbidity score and Kanorfsky performance status. Brain metastasis at the time of diagnosis was more frequent in the group who received gastric acid suppressive therapy compared with the group who did not receive gastric acid suppressive therapy (61.8% v 35.3% respectively, p= 0.001). The median overall survival in the total patient population was 13.1 months (95%CI 11.7-15.2 months). On multivariate analysis, presence of visceral metastasis at diagnosis was associated with a worse overall survival (HR: 1.53, 95% CI:1.10-2.13 p value: 0.012). However a Karnofsky performance score of 90-100 was associated with an improved overall survival (HR: 0.69, 95% CI; 0.49-0.97 p value: 0.031). The median overall survival OS in patients with gastric acid suppressive therapy was 11.9 months (95%CI: 9.90-16.94 months) and 14.5 months (95%CI: 11.74-15.95 months) in the group not receiving gastric acid suppressive therapy. (HR: 0.98, 95% CI: 0.69-1.40 p value: 0.934)

      Conclusion:
      Although the group of patients who were treated with gastric acid suppressive therapy had a numerically poorer overall survival compared to the group who did not receive gastric acid suppressive therapy, this difference was not statistically significant. Based on the our analysis, the use of gastric acid suppressive therapy concurrent with EGFR tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer harboring EGFR mutations did not affect overall survival.

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    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P2.01-019 - Effect of EGFR Mutation Status on Graded Prognostic Assessment for Non-Small Cell Lung Cancer and Brain Metastases (ID 1055)

      09:30 - 17:00  |  Author(s): N.B. Kumarakulasinghe

      • Abstract
      • Slides

      Background:
      The aim of this study is to refine the existing lung cancer graded prognostic assessment (GPA) index by analysing a cohort of patients with non-small cell lung cancer (NSCLC) tested for epidermal growth factor receptor (EGFR) mutation status and newly diagnosed brain metastases.

      Methods:
      We used the pathology registries of two institutions to identify 259 eligible patients diagnosed with brain metastases secondary to NSCLC between 2006 and 2014. We linked the electronic medical records of these patients to the National Death Registry. Survival is defined as from date of first treatment for brain metastases or date of brain metastases diagnosis for patients on best supportive care till death. We analysed the prognostic factors significant for survival by multivariate Cox regression and recursive partitioning analysis (RPA).

      Results:
      Significant prognostic factors identified by multivariate Cox regression and RPA were age, Karnofsky performance status (KPS), presence of extra-cranial metastases (ECM), number of brain metastases (BM) and presence of sensitizing EGFR mutations. Patients who were age 70 years old and above (Hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.07-2.01, reference (ref) age < 70 years old); with KPS score 70-80 (HR 2.37, 95%CI 1.69-3.34, ref KPS 90-100); with KPS score < 70 (HR 4.34, 95%CI 2.90-6.51, ref KPS 90-100); ECM present (HR 1.82, 95%CI 1.27-2.62, ref no ECM); having two or more BM (HR 1.40, 95%CI 1.01-1.95, ref less than two BM) and absence of sensitizing EGFR mutations (HR 1.97, 95%CI 1.49-2.61, ref sensitizing EGFR mutations present) were poor prognostic factors. There was a robust separation of survival curves between GPA score 0-1.0 (median survival (MS) 2.1 months), GPA score 1.5-2.0 (MS 6.3 months) and GPA score 2.5-3.0 (MS 14.1 months). The proposed modified GPA index is shown in below table.

      Proposed modified GPA index
      Prognostic factors / score 0 0.5 1.0
      Age Group ≥70 years old <70 years old -
      KPS <70 70-80 90-100
      ECM Present - Absent
      No. of BM ≥2 0-1
      Sensitising EGFR mutations Absent - Present


      Conclusion:
      EGFR mutation status is a significant prognostic factor and should be considered in the design of lung-cancer GPA index. The proposed modified GPA index need to be validated with an independent dataset.

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