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H. Suzuki



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    OA08 - Targeted Therapies in Brain Metastases (ID 381)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
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      OA08.05 - Efficacy and Cerebrospinal Fluid Concentration of Afatinib in NSCLC Patients with EGFR Mutation Developing Leptomeningeal Carcinomatosis (ID 4210)

      16:00 - 17:30  |  Author(s): H. Suzuki

      • Abstract
      • Presentation
      • Slides

      Background:
      Afatinib (AFA) is an effective treatment in advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutation. However, there were few reports about the cerebrospinal fluid (CSF) penetration rate and the efficacy for central nervous system (CNS) metastasis. Therefore, we conducted the study to evaluate the CSF penetration rate and efficacy of AFA in NSCLC patients harboring EGFR mutation with leptomeningeal carcinomatosis (LC).

      Methods:
      Eligibility criteria included performance status (PS) 0-3, aged 20 years or older, pathologically proven NSCLC, harboring EGFR mutation, with LC, adequate organ function, and written informed consent. Patients received AFA (40mg/body every day). We analyzed the blood and CSF level of AFA before administrating AFA on the eighth day. The primary endpoint was the CSF penetration rate. Secondary endpoints included objective response rate (ORR), progression free survival (PFS), overall survival (OS), and safety profile.

      Results:
      A total of 11 patients were enrolled. And we could analyze the blood level in10 patients and the CSF level in 8 patients. Median patients-age was 66 years old. All patients were adenocarcinoma. In EGFR mutation status, 5 patients had exon 19 deletion, 3 had L858R and 3 had minor (exon18) mutation. The patients with PS 2 were 3 patients and PS 3 were 4 patients. Almost all patients received AFA after third-line or more line chemotherapy. The blood level was the Median 88.2 ng/ml (range: 30.4-373), the CSF level was Median 1.4 ng/ml (range: 0.39-2.85) and the CSF penetration rate was Median 1.65% (range: 0.1-9.25). The ORR is 27.3%, and two of three petients with exon 18 mutation showed the partial response. Median OS was 3.8 months (95%CI: 1.1-13.1) and median PFS was 2.0 months (95%CI: 0.6-5.8). Hematological toxicity was mild, however we have to take care of severe diarrhea and skin toxicities, especially in patients with poor PS.

      Conclusion:
      The median CSF penetration rate (1.65%) of AFA were higher than the penetration rate in previous case report. Although the efficacy for EGFR mutation positive patients with LC was moderate, the promising efficacy for the patient with LC harboring EGFR exon 18 mutation was demonstrated. And we have to take care of diarrhea and skin toxicities, especially in the patients with poor PS.

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    P3.02b - Poster Session with Presenters Present (ID 494)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02b-087 - Dose Escalation Study of CDDP plus PEM with Erlotinib and Bev Followed by PEM with Erlotinib and Bev for Non-SQ NSCLC Harboring EGFR Mutations (ID 5891)

      14:30 - 15:45  |  Author(s): H. Suzuki

      • Abstract

      Background:
      Cisplatin and pemetrexed with or without bevacizumab is the most effective treatment for advanced non-squamous NSCLC patients without EGFR mutations. On the other hand, erlotinib and bevacizumab is the most effective treatment for advanced non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations. There have not been any evidence-based studies of erlotinib and bevacizumab in combination with platinum-doublet therapy for advanced non-squamous NSCLC patients with EGFR mutations, therefore we performed Quartet trial to determine the safety and efficacy of quartet chemotherapy with cisplatin plus pemetrexed with erlotinib and bevacizumab as a first-line treatment.

      Methods:
      Patients received escalated doses of cisplatin plus pemetrexed with erlotinib and bevacizumab every 3 weeks for 4 cycles. We examine the dose limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) and recomended dose (RD) of quartet chemotherapy.

      Results:
      10 patients were enrolled in Quartet trial. 3 patients were men and 7 patients were women. Median age was 69 (65-75) years old. 4 patients had exon19 mutation and 6 patients had exin21 mutation. Of a total of 10 patients, 8 patients received maintenance therapy without unexpected or cumulative toxicities. One of six patients experienced DLT (vagal reflex of grade3) at 60mg/m[2] cisplatin plus 500 mg/m[2 ]pemetrexed with 150mg erlotinib and 15mg/kg bevacizumab (RD). Four patients experienced no DLT, however one patient experienced severe toxicities (gastrointestinal hemorrhage of grade3) during 2 cycle of induction chemotherapy and dose reduction was needed at 75mg/m[2] cisplatin plus 500 mg/m[2 ]pemetrexed with 150mg erlotinib and 15mg/kg bevacizumab (MTD). In DLT phase, most frequent adverse events were nausea, anorexia and fatigue. In Quartet trial study, the overall response rate was 100%. Furthermore, progression free survival and overall survival were not reached.

      Conclusion:
      This quartet chemotherapy was a tolerable and effective regimen, and we determined the combination of cisplatin at 60mg/m[2] plus 500 mg/m[2 ]pemetrexed with 150mg erlotinib and 15mg/kg bevacizumab was RD and the combination cisplatin at 75mg/m[2 ]was MTD in chemotherapy-naïve advanced non-squamous NSCLC patients harboring EGFR mutations (UMIN000012536).