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F. Imamura



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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 3
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      P2.10-007 - Phase II trial of Pemetrexed and Carboplatin followed by Pemetrexed continuation-maintenance therapy in previously untreated advanced non-small cell lung cancer (ID 679)

      09:30 - 09:30  |  Author(s): F. Imamura

      • Abstract

      Background
      Survival benefits of pemetrexed for advanced non-squamous non-small cell lung cancer (NSCLC) have been demonstrated in both switch- and continuation-maintenance settings after platinum-based induction. A phase III trial (PARAMOUNT) comparing pemetrexed maintenance with best supportive care after 4 cycles of induction pemetrexed plus cisplatin in non-squamous NSCLC patients demonstrated benefits both in progression-free-survival (PFS) and overall survival (OS) by pemetrexed continuation-maintenance. However, it remained undetermined whether pemetrexed could improve survival when it was continued to administer after carboplatin plus pemetrexed induction. We conducted a phase II study to evaluate the efficacy and safety of this regimen.

      Methods
      Thirty-four chemonaïve patients with stage IIIB/IV or postoperative recurrent non-squamous NSCLC received carboplatin (area under the concentration-time curve 6 mg/mL/min, day 1) plus pemetrexed (500 mg/m[2], day 1) every 3 weeks. Non-progressive patients after 4 cycles of induction received pemetrexed maintenance (500 mg/m[2], day 1) every 3 weeks until disease progression or unacceptable toxicity. The primary objective was to investigate 1-year survival rate. Secondary objectives were to investigate the safety, the objective response rate (ORR) during induction chemotherapy and PFS, defined as the time from enrollment to disease progression or death.

      Results
      From December 2009 to March 2011, a total of 34 patients were enrolled. The median follow-up time was 20.9 months (range, 2 to 32.3). At the time of the data collection, 19 patients were dead, 13 still alive, 2 lost follow-up. Twenty-five patients (73.5%) completed induction and 22 patients (64.7%) received maintenance therapy. The 1-year survival rate was 70.3% (95% CI, 53.0 to 83.2). The 2-year survival rate was 45.5% (95% CI, 28.7 to 63.5). The median PFS and OS were 5.2 months (95% CI, 4.1 to 8.2) and 23.0 months (95% CI, 15.5 to not available) from enrollment in all 34 patients, in addition 9.0 months (95% CI, 5.2 to 12.1) and 24.3 months (95% CI, 17.8 to not available) from the start of maintenance therapy in 22 patients who proceeded to maintenance therapy. The objective response rate and the disease control rate were 32.4% and 88.2%. The incidental rates of grade 3 or more severe adverse events were low except for one case of grade 5 pneumonitis. A multivariate analysis of 21 patients who received maintenance therapy with any tumor regression showed that the longer time to the best response achievement, positive epidermal growth factor receptor mutation status and better Karnofsky performance status contributed to achieve longer PFS.

      Conclusion
      Pemetrexed continuation-maintenance following pemetrexed plus carboplatin induction is a promising treatment for chemonaïve patients with advanced non-squamous NSCLC because of its good efficacy and less cumulative toxicities. This regimen could be substitutable for pemetrexed continuation-maintenance following cisplatin-based induction.

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      P2.10-014 - A phase II study of bevacizumab in combination with carboplatin and paclitaxel in patients with non-squamous (Non-Sq) non-small-cell lung cancer (NSCLC) harboring Mutations of Epidermal Growth Factor Receptor (EGFR) gene after failing First-line EGFR-Tyrosine Kinase Inhibitors (TKIs) Hanshin Oncology Group 0109 (ID 1054)

      09:30 - 09:30  |  Author(s): F. Imamura

      • Abstract

      Background
      EGFR-TKIs’ mono-therapy is one of the standard 1[st] line therapy for NSCLC harboring EGFR gene mutations. Although platinum doublet ± bevacizumab recommended for 2nd line therapy after failing EGFR-TKIs in National Comprehensive Cancer Network guideline, there is little information of these setting. Therefore, we planned prospective phaseⅡ study to evaluate the efficacy and safety of bevacizumab in combination with carboplatin and paclitaxel(PCB) for EGFR-TKIs resistant Non-Sq NSCLC.

      Methods
      In multicenter phase II trial, we recruited non-squamous NSCLC harboring EGFR gene mutation after failing EGFR-TKIs. Key eligibility criteria were as follows: Non-Sq NSCLC with EGFR mutation, failure of 1[st] line EGFR-TKIs, stageIIIB or IV or recurrence after surgery, measurable lesion, age 20 or over, ECOG Performance status (PS) 0 or 1, adequate organ function. Clinically significant hemoptysis, symptomatic brain metastasis, uncontrollable hypertension, interstitial pneumonia were excluded. Patients received carboplatin (AUC=6/5), paclitaxel (200mg/m2), bevacizumab (15mg/kg) intravenously on day1 every 3 weeks for three to six cycles, and bevacizumab was administered every 3 weeks until disease progression or intolerable toxic effects. Primary endpoint was response rate (RR) and secondary endpoints were progression free survival (PFS), overall survival (OS), disease control rate (DCR) and safety.

      Results
      A total of 31 patients were assigned between March 2010 and February 2013. One patient was excluded because of unfitted eligibility criteria. Therefore, we analyzed thirty patients’ data. Median age was 60 years (45~74), male/female : 11/19, PS 0/1 : 9/21, non-smoker/smoker : 18/12, EGFR mutation status exon19 del/exon21 L858R : 20/11, 1[st] line EGFR-TKIs gefitinib/erlotinib/other : 22/7/1. RR : 40% (95%CI:22%-58%), DCR : 83% (95%CI:70%-97%), PFS : 6.0 month (95%CI:4.8-12.2). Major severe adverse event (Grade 3,4) were one patient with dyspnea (G4), 6 with fever neutropenia (G3) and 3 patients with hyper tension (G3). There was no grade 5 adverse event.

      Conclusion
      In patients with Non-Sq NSCLC harboring EGFR gene mutation failed 1[st] line EGFR-TKIs, RR of 2[nd] line PCB therapy was lower than it was in 1[st ]line phase II study of PCB in Japan, but same RR of E4599 study. Safety was similar to previous reports. We considered PCB therapy is one of the treatment option in 2[nd]-line for patient with EGFR-TKIs resistant Non-Sq NSCLC.

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      P2.10-028 - Efficacy and safety of erlotinib in elderly versus non-elderly patients: analysis of the POLARSTAR study of 9,909 Japanese non-small cell lung cancer (NSCLC) patients treated with erlotinib. (ID 1591)

      09:30 - 09:30  |  Author(s): F. Imamura

      • Abstract

      Background
      Compared with younger patients, elderly NSCLC patients are often considered unfit for standard chemotherapy due to increased chemotherapy-related toxicity, more comorbidities, and the consequent deterioration in patient quality of life. Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has demonstrated survival benefits with good tolerability in previously treated NSCLC patients regardless of EGFR mutation status. Erlotinib has become a standard treatment for this indication. As it is well tolerated compared with cytotoxic agents, erlotinib is also expected to be a valid treatment option for previously treated elderly NSCLC patients. This analysis of the POLARSTAR surveillance study compared the efficacy and safety of erlotinib treatment for elderly versus non-elderly patients.

      Methods
      From December 2007 to October 2009 all recurrent/advanced NSCLC patients in Japan treated with erlotinib were enrolled onto the POLARSTAR surveillance study. Erlotinib efficacy and safety data were analyzed by age group: Group A <75 years; Group B 75–84 years; and Group C ≥85 years. Kaplan–Meier methods were used to estimate median progression-free survival (PFS). All adverse event reports were collected and graded using the NCI-CTCAE version 3.0 and coded using MedDRA version 14.1.

      Results
      Of 9,909 patients evaluated, 9,907 were eligible for safety assessment (Group A, n=7,848; Group B, n=1,911; Group C, n=148). Baseline characteristics (including histology, smoking status and performance status [PS]) were well-balanced between groups. Non-hematologic toxicities are shown (Table). Grade 1–4 hematologic toxicities (neutropenia/leukopenia/anemia/thrombocytopenia) were observed at <1.0% in each group. One patient had grade 5 anemia (Group A) and one patient had grade 5 thrombocytopenia (Group B). A total of 9,651 patients were eligible for efficacy assessment. The median PFS was 65 days for Group A (n=7,701), 74 days for Group B (n=1,815) and 72 days for Group C (n=135). In patients with clinical features associated with better EGFR TKI efficacy (adenocarcinoma/non-smoker/PS 0–2/second- or third-line setting/EGFR TKI naïve) the median PFS was 176 days (Group A, n=651), 213 days (Group B, n=180), and 341 days (Group C, n=14). Figure 1

      Conclusion
      Efficacy and tolerability of erlotinib treatment for elderly patients (≥75 years) with previously treated NSCLC was similar to that seen in younger patients. Erlotinib could be considered as standard therapy for elderly NSCLC patients in second- or later line treatment settings.