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H. Mizugaki



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    P1.09 - Poster Session 1 - Combined Modality (ID 212)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P1.09-010 - Impact of the presence of EGFR mutation on the definitive chemoradiotherapy in patients with locally advanced non-small cell lung cancer: pattern of relapses and survival analyses in 198 patients (ID 1227)

      09:30 - 09:30  |  Author(s): H. Mizugaki

      • Abstract

      Background
      The epidermal growth factor receptor (EGFR) mutational status is an important biomarker in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the frequency and clinical significance of EGFR mutation in patients with potentially curable locally advanced NSCLC (LA-NSCLC) who are eligible for definitive chemoradiotherapy (CRT).

      Methods
      Between Jan 2001 and Dec 2010, we conducted analysis for the presence of EGFR mutations, in consecutive non-squamous NSCLC (mainly in adenocarcinoma) patients who were eligible for CRT. The response rate (RR), progression-free survival (PFS), 2-year progression-free rate, first recurrent sites, and overall survival were investigated according to the EGFR mutational status.

      Results
      A total of 528 patients received CRT at the National Cancer Center Hospital during the study period, of which 274 were diagnosed as having non-squamous NSCLC (mainly adenocarcinoma). Sufficient specimens for mutational analyses could be obtained from 198 patients, and EGFR mutations were found at a frequency of 17% in these patients. In addition to the well-known characteristics of NSCLC patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller (T1/2) primary lesions was also higher in the patients carrying mutated EGFR than in those carrying wild-type EGFR. Patients carrying mutated EGFR showed similar RR (79% vs. 76%), median PFS (11.8 m vs. 10.6 m) and 2-year progression-free survival rate (22% vs. 30%) as compared to those carrying wild-type EGFR. Local recurrence as first relapse occurred less frequently in patients carrying mutated EGFR than in those carrying wild-type EGFR (4% vs. 21%). A majority of the patients with mutated EGFR showing disease progression received EGFR-TKIs (55%), and these patients showed a longer post-progression survival and a higher 5 year survival rate (50% vs. 34%) than the patients with wild-type EGFR.

      Conclusion
      Among the LA-NSCLC patients eligible for definitive CRT who were included in this analysis, 17% harbored EGFR-activating mutations in the carcinoma specimens. Although definitive CRT was similarly effective in both patients with mutated EGFR and wild-type EGFR, substantially lower frequency of local relapse was noted in the patients carrying mutated EGFR. Among the LA-NSCLC patients harboring EGFR mutations who developed disease progression, those treated with EGFR-TKIs showed a longer post-progression survival and overall survival as compared to those who did not receive EGFR-TKIs.

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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-040 - Phase 1 study of ipilimumab in combination with paclitaxel/carboplatin in patients with non-small cell lung cancer (ID 2775)

      09:30 - 09:30  |  Author(s): H. Mizugaki

      • Abstract

      Background
      Ipilimumab is a fully human IgG1 monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) and augments antitumor T-cell responses. In a global phase 2 study in subjects with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), ipilimumab administrated in a phased schedule in combination with paclitaxel/carboplatin, improved immune-related progression-free survival with an acceptable safety profile. A pronounced benefit was observed in squamous NSCLC. We conducted the phase 1 study of ipilimumab in combination with paclitaxel/carboplatin in Japanese patients with NSCLC.

      Methods
      Target population was Japanese subjects with stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC. Patients received ipilimumab 3 mg/kg or 10 mg/kg (starting at Cycle 3) in addition to paclitaxel 175 mg/m2 and carboplatin AUC=6 every 3 weeks for up to 6 cycles. Dose limiting toxicity (DLT) was evaluated during the first two cycles of ipilimumab administration (Cycle 3 and Cycle 4). The recommended dose (RD) was defined as the highest dose at which no more than 2 out of 6 ipilimumab-treated patients experienced a DLT.

      Results
      A total 15 patients were enrolled and 12 patients received ipilimumab (female/male=1/11, range of age =53-70, stage IIIB/IV/recurrent=0/9/3, squamous/non-squamous= 1/ 11, ipilimumab 3 mg/kg / 10 mg/kg=6/6). DLTs were observed in 2 out of 6 ipilimumab-treated patients in ipilimumab 3 mg/kg arm (febrile neutropenia, amylase increased / 1patient, thrombocytopenia / 1patient) and 1 out of 6 ipilimumab -treated patients in ipilimumab 10 mg/kg arm (entercolitis, total-bilirubin increased, lipase increased). Of 10 patients evaluable for tumor response based on RECIST criteria, partial response and stable disease were achieved in 6 and 4 patients, respectively.

      Conclusion
      For Japanese patients with NSCLC, the RD of ipilimumab in combination with chemotherapy was identified as 10 mg/kg and it demonstrated acceptable safety profile and potential efficacy. Two global Phase 3 studies are ongoing in subjects evaluating ipilimumab 10 mg/kg in combination with chemotherapy in advanced squamous NSCLC (with carboplatin/paclitaxel) and extensive stage SCLC (with etoposide/platinum).

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    P3.13 - Poster Session 3 - SCLC (ID 202)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.13-002 - Stereotactic radiosurgery for brain metastases after prophylactic cranial irradiation in limited disease small-cell lung cancer (ID 1137)

      09:30 - 09:30  |  Author(s): H. Mizugaki

      • Abstract

      Background
      Brain metastases are very common in patients with small-cell lung cancer (SCLC). Prophylactic cranial irradiation (PCI) has been shown to reduce the incidence of brain metastases and to improve overall survival in patients with limited-disease SCLC (LD-SCLC). However, brain metastases are often observed after PCI, and the optimal treatment for these brain metastases is still unclear. The present study investigated the recurrence of brain metastases after PCI in patients with LD-SCLC and the therapeutic efficacy of stereotactic radiosurgery for these metastases.

      Methods
      Between December 2000 and December 2012, 228 patients with LD-SCLC were treated and 98 of these patients with a complete response (CR) or a near CR to chemoradiotherapy underwent PCI at the National Cancer Center Hospital. We retrospectively reviewed the medical records and imaging data for these 98 patients.

      Results
      Twenty-four (24%) of the 98 patients developed brain metastases after PCI. The characteristics of the 24 patients were as follows: median age, 62 years (49-72 years), male/female, 21/3; performance status 0/1/2, 2/16/6. Twelve (50%) of the 24 patients had cranial recurrences only. Twelve patients had single brain metastases, and 12 patients had multiple lesions. Nine patients had neurological symptoms due to brain metastases. The median period after PCI until the appearance of the metastases was 9.9 months (1.1-34.9 months). Fifteen (63%) of the 24 patients underwent stereotactic radiosurgery (gamma knife radiosurgery [GKRS]), and one patient received whole brain radiotherapy. Six patients were treated with chemotherapy plus best supportive care (BSC), and two patients underwent BSC alone. The 15 patients who received GKRS had brain metastases with/without extracranial lesions (7 with, 8 without); three were symptomatic, and 12 were asymptomatic. The median number of brain metastases at the time of the first GKRS was one (range, 1-4). The local control rate of the lesions treated with GKRS was 86.7% (complete response in 3 patients, partial response in 7 patients, and stable disease in 3 patients). Five patients underwent further GKRS because of newly developing brain metastases (median: 4 times, range: 2-7 times). The median intracranial control time of the 15 patients was 6.8 months. The median survival time of the 15 patients was 29.3 months after the initial diagnosis, 13.7 months after the development of brain metastases, and 12.7 months after the treatment of GKRS. The median survival time of the patients without extracranial lesions was 20.2 months after the development of brain metastases and tended to be longer than that of the patients with extracranial lesions (12.6 months). Severe adverse events arising from GKRS were not observed in this series.

      Conclusion
      Stereotactic radiosurgery may be an effective option as a salvage therapy for brain metastases after PCI in patients with LD-SCLC.