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S. Yagishita



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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 - 16:30  |  Author(s): S. Yagishita

      • 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 - 16:30  |  Author(s): S. Yagishita

      • 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).