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H. Yoshioka



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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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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): H. Yoshioka

      • 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.

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    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P3.09-007 - Update data of biomarker analysis of WJOG4107 (A randomized phase II trial of adjuvant chemotherapy with S-1 versus CDDP+S-1 for resected stage II-IIIA non-small cell lung cancer (NSCLC)) (ID 1504)

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

      • Abstract

      Background
      We conducted a randomized phase II trial for patients with resected stage II-IIIA NSCLC comparing postoperative oral S-1 (80 mg/m2/day for consecutive 2 weeks q3w for 1 year) (S) (N=100) or cisplatin (CDDP) (60 mg/m2 day1) plus oral S-1, (80 mg/m2/day for 2 weeks) q3w for 4 cycles (PS)(N=100). We reported that disease free survival rate at 2 years (DFS@2) (95% confidence interval: CI), a primary endpoint, was 66 (55-74) % for S and 58 (48-67)% for PS. Here, we report the preliminary results of preplanned biomarker analysis, a co-primary endpoint, to identify molecules whose expression is significantly associated with patient outcome.

      Methods
      　cDNA extracted from macro-dissected formalin-fixed paraffin-embedded specimens were available for 197/200 patients. Thirty-one genes including those whose expressions have been potentially associated with　CDDP (e.g. ERCC1, XRCC1, BRCA1, GSTpi, HMG1, TBP) or fluorouracil (FU) sensitivity (TS, DHFR, DPD, UMPS, UPP1) were measured by QGE analysis (MassArray, Sequenom, CA). Additional analysis are being performed to assess ERCC1 isoform expression with an isoform-specific TaqMan probe (Applied Biosystems, CA). The expression of each gene was dichotomized according to its median value.

      Results
      Molecules such as ERCC1 and GSTpi whose expression have been previously associated with CDDP sensitivity did not emerge as predictive markers (P=0.7908, 0.6406, respectively). We quantitated ERCC1 by isotype (202 and 204 cannot be distinguished). There was a trend in patients with high 201 or 202/204, CDDP/S-1 was worse than S-1.

      Conclusion
      Quantitation of ERCC1 by isotype may define a patient subset that would benefit from postoperative platinum therapy.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-007 - Preliminary safety results of MONET-A: A Prospective, Asian Phase 3, Randomized, Placebo-controlled, Double-blind Trial of the Investigational agent Motesanib in Combination with Paclitaxel and Carboplatin for Asian patients of Advanced Non-squamous Non-small Cell Lung Cancer (ID 889)

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

      • Abstract

      Background
      Inhibition of the vascular endothelial growth factor receptor (VEGFR) pathway appears to be an effective treatment strategy for frontline non-small cell lung cancer (NSCLC), but small molecule VEGFR kinase inhibitors have failed to show survival benefit. Motesanib is an orally administrated small molecule antagonist of VEGFR 1, 2, and 3, platelet-derived growth factor receptor (PDGFR), and stem cell factor receptor (c-kit). In a subgroup analysis of Asian patients (n = 227) from the global phase 3 study (MONET-1), treatment of motesanib in combination with paclitaxel and carboplatin demonstrated significant improvements in overall survival (HR, 0.65; 95% CI, 0.46-0.91), progression free survival (HR, 0.59; 95% CI, 0.44-0.79), and overall response rate compared to placebo. To prospectively evaluate efficacy and safety of motesanib in Asian patients with NSCLC, this phase 3 study has initiated.

      Methods
      Stage IV/recurrent non-squamous NSCLC patients without prior chemotherapy receive oral motesanib (125 mg) or placebo once daily in combination with paclitaxel (200 mg/m[2]) and carboplatin (AUC = 6) every 3 weeks up to 6 cycles and continue motesanib or placebo until disease progression, consent withdrawal, or unmanageable adverse event. ECOG performance status 0 or 1 are eligible for this study regardless of epidermal growth factor receptor (EGFR) mutation status. Patients with untreated or symptomatic central nervous system metastases are excluded. Approximately 400 patients will be randomized in a double-blind 1:1 ratio to motesanib or placebo. Stratification factors include EGFR mutation status, weight loss of ≥ 5% in the previous 6 months, and region. This MONET-A trial will be assessed twice by the Independent Data Monitoring Committee (IDMC), at the time 50 and 150 patients complete their first cycle for unblinded safety data.

      Results
      This study initiated in July 2012 and is being conducted in Japan, Korea, Taiwan, and Hong Kong. The enrollment is ongoing. First evaluation by IDMC was performed using the data as of 26 December 2012. A total of 64 patients were enrolled and 63 patients (63 Japanese; median age, 64.5 years) received study treatment. All the blinded patients who received study treatment experienced adverse events (AEs); Grade 3 to 5 AEs were reported in 38 patients (60.3%). Common AEs included alopecia (63.5%), peripheral sensory neuropathy (57.1%), and decreased appetite (50.8%). 7 patients had 8 serious AEs (SAEs). SAEs considered to be related to blinded study drug were cholecystitis in 2 patients, gastric ulcer haemorrhage, nausea, and upper gastrointestinal haemorrhage in 1 patient. A treatment-related fatal AE (interstitial lung disease) was reported in one patient (blinded). AEs leading to permanent discontinuation of unblindedunblinded study drug (motesanib or placeco) were cholecystitis (Grade 2), liver injury (Grade 3), purpura (Grade 2), rash (Grade 3), eye haemorrhage (Grade 2), upper gastrointestinal haemorrhage (Grade 3), and gamma-glutamyltransferase increased (Grade 4).

      Conclusion
      The first IDMC recommended continuation of the study after the review of unblinded data of 63 patients. Updated safety data will be presented after the second IDMC (JapicCTI-121887).