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K. Kiura



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    OA11 - Angiogenesis in Advanced Lung Cancer (ID 387)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
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      OA11.02 - Randomized Phase 1b/3 Study of Erlotinib plus Ramucirumab in First-Line EGFR Mut + Stage IV NSCLC: Phase 1b Safety Results (ID 3827)

      11:00 - 12:30  |  Author(s): K. Kiura

      • Abstract
      • Presentation
      • Slides

      Background:
      Ramucirumab, an antiangiogenic IgG1 VEGFR2-targeted monoclonal antibody, and erlotinib, an EGFR tyrosine kinase inhibitor, are both active in advanced NSCLC. This global phase 1b/3 study (NCT02411448) will assess safety, tolerability and efficacy of the combination of ramucirumab with erlotinib in previously untreated patients with EGFR mutation-positive stage IV NSCLC. Here we report phase 1b safety results.

      Methods:
      Eligible patients with ECOG PS 0-1, an activating EGFR mutation, and previously untreated stage IV NSCLC received ramucirumab 10 mg/kg intravenously on day 1 of repeating 14-day (± 3 days) cycle and erlotinib 150 mg orally daily. Treatment continued until disease progression or unacceptable toxicity. The primary objective of part A was to assess the safety and tolerability, in terms of dose limiting toxicities (DLT), of adding the recommended dose of ramucirumab for phase 3 (part B) to standard dose erlotinib. Data were analyzed separately for Japan (JP) (cohort 1) and US/EU (cohort 2). The DLT assessment occurred during the first 2 cycles (approximately 28 days).

      Results:
      As of Dec 16th, 2015, 14 patients were treated in the phase 1b part of this trial and 12 were DLT evaluable (6 JP; 6 US/EU). Overall, 6 grade (Gr) 3 treatment-emergent adverse events (TEAE) were noted, with at least one TEAE in 5 patients; no serious adverse events or Gr 4-5 TEAEs occurred. In the JP cohort the median age was 73 (64-79), 57% had ECOG PS 1 and 29% had a history of smoking. Four patients (57%) experienced a Gr 3 TEAE, of which one was a DLT (elevation of alanine aminotransferase) while the others (hypertension [n=2], dermatitis acneiform, and diarrhea) were not DLTs. In the US/EU cohort the median age was 71 (31-83), 86% had ECOG PS 1, and no patients had a history of smoking. One patient experienced Gr 3 TEAE of rash; no DLTs were observed in this cohort.

      Conclusion:
      Enrollment on the phase 1b portion of this trial is complete and the safety results were consistent with previous combinations of antiangiogenic/erlotinib in this patient population. No unexpected toxicities were identified. Phase 3 enrollment has been initiated maintaining the dose of ramucirumab at 10 mg/kg Q2W.

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    P2.02 - Poster Session with Presenters Present (ID 462)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 2
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      P2.02-009 - Clinical Outcomes of Induction Chemoradiotherapy with High Dose Chest Radiation for Locally Advanced Non-Small Cell Lung Cancer Patients (ID 4362)

      14:30 - 15:45  |  Author(s): K. Kiura

      • Abstract

      Background:
      In the treatment of patients with locally-advanced non-small cell lung cancer (LA-NSCLC), we usually apply chemoradiotheraphy (CRT) consisted of docetaxel and cisplatin with concurrent 40-60 Gy radiation therapy. The radiation dose of 60 Gy is generally planned in the case of definitive CRT. On the other hand, the radiation dose of 46 Gy is planned in the case of induction CRT, considering the safety of surgery. In the induction CRT, if the treatment response is poor and complete resection is supposed to be difficult, additional radiation is performed. In this study, we examined the safety and clinical outcome of lung resection after induction CRT using high-dose radiation in patients with LA-NSCLC.

      Methods:
      One hundred and eighteen patients with LA-NSCLC who underwent induction CRT followed by surgery between March 1999 and December 2014 in our hospital were reviewed. We categorized those patients into low-dose radiation group who received less than 60 Gy of radiation (n=105) and high-dose radiation group who received more than 60 Gy of radiation (n=13). We compared postoperative outcomes between these two groups applying match-paired analysis with using propensity score.

      Results:
      One hundred and eighteen cases consisted of 91 males and 27 females, and the average age was 60 years. Eleven patients had stage IIB disease, 73 patients had stage IIIA disease, and 34 patients had stage IIIB disease before CRT. The background between low-dose group and high-dose group was similar. There were no significant differences in the mortality (0.8% vs 0% in low-dose group and high-dose groups), the incidence of postoperative complication (57% vs 77%), and post-operative hospital days (median 22 vs 28 days) between each group. In addition, there were no significant differences in the 5-year OS rates (73% vs 77% in low-dose group and high-dose groups, p =0.66), and the 5-year DFS rates (56% vs 77%, p =0.11) between each group, even when we applied matched-paier analyses.

      Conclusion:
      This study showed that lung resection after induction CRT using high-dose radiation for LA-NSCLC patients had been performed safely with equivalent prognosis compared with that using low-dose radiation.

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      P2.02-054 - Impact of Prognostic Nutrition Index for Induction Chemoradiotherapy Followed by Surgery in Locally Advanced Non-Small Lung Cancers (ID 4607)

      14:30 - 15:45  |  Author(s): K. Kiura

      • Abstract

      Background:
      The preoperative nutritional and immunological statuses have an important impact in predicting the clinical outcome of surgery. Induction chemoradiotherapy (iCRT) followed by surgery is one of treatment options for locally advanced (LA) non-small cell lung cancers (NSCLCs) although there is a risk for increasing postoperative complications with protracted would healing. A prognostic nutritional index (PNI), calculated using serum albumin levels and peripheral lymphocyte count, has been used to predict the clinical outcome of various cancers including early stage NSLCCs but not LA-NSCLC after iCRT. In this study, we investigated the impact of PNI on clinical outcome of iCRT followed by surgery in the patients with LA-NSCLCs.

      Methods:
      During 2009 to 2014, 70 patients underwent iCRT followed by surgery in Okayama University Hospital. We retrospectively calculated the PNI at (1) pre-iCRT, (2) pre-operation (Ope), and (3) post-Ope (about one month later) and reviewed the medical records.

      Results:
      The median age was 63 years old (range 34 – 78) and 53 patients were male. Forty-three patients were adenocarcinomas and 24 were squamous cell carcinomas. Clinical stages were IIA (n =3), IIB (n = 6), IIIA (n = 44), IIIB (n = 15), and IV (n = 2). Main regimen of iCRT was CDDP / DOC with concurrent radiotherapy (46 gray). Treatment responses were partial response (n = 44), no change (n = 24), and progressive disease (n = 2). Lung resections were lobectomy (n = 66), bi-lobectomy (n = 6), and pneumonectomy (n = 2) and additional procedure such as combined resection was performed in 43 patients (61%). Pathological responses were Ef1 (n = 20), Ef2 (n = 29), and Ef3 (n = 21). The median values of PNI were significantly decreased during treatment course [50 (39 – 71) in pre-ICRT, 45 (31 – 58) in pre-Ope, and 41 (24 – 54)]. We defined the cutoff value of PNI as 45 based on previous reports. The patients with high PNI (more than 45) in pre-iCRT showed significantly better prognosis than those with low PNI (3 years overall survival rate, 85% in high PNI vs 53% in low PNI, P = 0.03).

      Conclusion:
      Pre-treatment nutritional and immunological statuses that were evaluated using PNI may affect clinical outcome of the patients who received the iCRT followed by surgery for LA-NSCLCs.

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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-086 - ASP8273 Tolerability and Antitumor Activity in TKI-Naïve Japanese Subjects with EGFRmut+ NSCLC: Preliminary Results (ID 4126)

      14:30 - 15:45  |  Author(s): K. Kiura

      • Abstract

      Background:
      ASP8273, an orally administered epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits EGFR-activating mutations, has demonstrated clinical activity in ongoing Phase 1/2 studies in subjects with EGFR mutation-positive non-small cell lung cancer (NSCLC).

      Methods:
      EGFR TKI-naïve adult subjects (≥20 years) with EGFR mutation-positive metastatic or advanced unresectable NSCLC were enrolled in this ongoing, open-label, Phase 2 single-arm study conducted in Japan (NCT02500927). Subjects received once-daily ASP8273 300 mg until discontinuation criteria were met. The primary endpoint was tolerability; the secondary endpoint was antitumor activity (defined by RECIST v1.1).

      Results:
      As of 23 February 2016, 31 subjects (12M/19F; median age 64 years [range: 31–82]) with EGFR mutation-positive NSCLC have been enrolled; 25 subjects (81%) were still on study. Based on local testing, 27 (87%) of the 31 enrolled subjects had an ex19del (n=13, 42%) or a L858R (n=14, 45%) EGFR activating mutation; 4 subjects (13%) had other EGFR activating mutations, including 2 subjects (6%) with L861Q. Moreover, 3 subjects (10%) were found to have both an activating mutation as well as the T790M resistance mutation. Tolerability of ASP8273 is presented in Table 1; gastrointestinal disorders were the most commonly reported treatment-emergent adverse events (eg, diarrhea [n=24, 77%], nausea [n=12, 39%], and vomiting [n=8, 26%)]). All subjects had at least 1 post-baseline scan; 1 subject (3%) achieved a confirmed complete response, 13 subjects (42%) had a confirmed partial response, and 15 subjects (48%) had confirmed stable disease (disease control rate: 94% [n=29/31]) per investigator assessment. Figure 1



      Conclusion:
      These preliminary data showed that ASP8273 300 mg is generally well tolerated and demonstrates antitumor activity in TKI-naïve Japanese subjects with EGFR mutation-positive NSCLC.