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S. Kudoh



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    O03 - NSCLC - Targeted Therapies I (ID 113)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O03.07 - Investigation of risk factors for developing interstitial lung disease (ILD) and poor prognostic factors for ILD death in Japanese patients with non-small-cell lung cancer (NSCLC): a final analysis of a large-scale erlotinib surveillance study (POLARSTAR) (ID 2208)

      11:35 - 11:45  |  Author(s): S. Kudoh

      • Abstract
      • Presentation
      • Slides

      Background
      A large-scale surveillance study (POLARSTAR) was implemented to investigate erlotinib safety and efficacy in Japanese patients, focusing on the pattern of occurrence of interstitial lung disease (ILD) and specific factors that may contribute to the onset of ILD in patients receiving erlotinib. The following risk factors for erlotinib-induced ILD have been previously reported: concurrent/previous ILD (adjusted hazard ratio [HR] =3.2), existing emphysema/chronic obstructive pulmonary disease (COPD) (HR=1.9) or lung infection (HR=1.6), smoking status (HR=2.2) and ECOG performance status 2–4 (HR=1.4). These were identified as the primary risk factors for ILD by multivariate analysis. The current analysis was carried out to identify factors linked with poor prognosis in terms of ILD-related death within the POLARSTAR surveillance study.

      Methods
      Enrolment of all patients in Japan receiving erlotinib for NSCLC took place between December 2007 and October 2009; the observation period was 12 months. All ILD-like events were assessed by an independent ILD review committee. ILD was defined as all ILD-like events excluding those events deemed non-ILD by the independent ILD review committee. Risk factors for poor prognosis concerning ILD death were analyzed by multivariate analysis using a logistic regression model.

      Results
      A total of 10,708 patients were enrolled by the data cut-off of 12 October 2009, with data available for 9,909 patients. The majority of ILD cases were reported within 4 weeks of receiving erlotinib. Among the 491 patients who experienced ‘ILD-like’ events, 93 could not be evaluated by the independent ILD review committee due to lack of imaging data; the remaining 398 patients were referred to the committee for evaluation. A total of 310 patients had confirmed ILD by the ILD review committee, based on image evaluation or clinical investigation; 125 had died as a result of ILD. These patients were assessed by multivariate analysis. Sixty-two events were deemed non-ILD and 26 events could not be evaluated due to a lack of clear clinical evidence (e.g. ILD could not be distinguished from progression or pneumonitis, or insufficient imaging data were available). The multivariate analysis identified ECOG performance status 2–4 (adjusted odds ratio [OR] =2.45 [95% CI 1.41–4.27]; p=0.0016), <50% remaining normal lung area (OR=3.12 [1.48–6.58]; p=0.0029) and interstitial pneumonia with concomitant honeycomb lung (OR=6.67 [1.35–32.94]; p=0.02) as poor prognostic factors for ILD death. However, pre-existing interstitial pneumonia by grade of severity was not identified as one of these factors. This result could be attributed to practical bias in this surveillance study, such as selection or treatment bias for patients with pre-existing interstitial pneumonia within the condition of careful dosage specified in the erlotinib label.

      Conclusion
      These final data from this large surveillance study in Japanese patients with recurrent and advanced NSCLC provide further information on the risk factors for poor prognosis with ILD, identifying those patients at greatest risk of ILD-related death. Improved awareness of these prognostic factors will help clinicians in monitoring those patients at highest risk.

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    O15 - NSCLC - Chemotherapy II (ID 109)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O15.05 - Randomized Phase III Trial of S-1 plus Cisplatin versus Docetaxel plus Cisplatin for Advanced Non-Small-Cell Lung Cancer (TCOG0701): Subgroup Analysis. (ID 1895)

      11:15 - 11:25  |  Author(s): S. Kudoh

      • Abstract
      • Presentation
      • Slides

      Background
      Docetaxel plus cisplatin (DP) is the only third-generation regimen that has demonstrated statistically significant improvements in overall survival and QOL by head-to-head comparison with a second-generation regimen (vindesine plus cisplatin) in patients with advanced non-small cell lung cancer (NSCLC). S-1 plus cisplatin (SP) has shown activity and good tolerability in phase II settings. Molecularly targeted agents including bevacizumab (BEV) have shown activity and safety in non-squamous (non-Sq) NSCLC.

      Methods
      Patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions were randomly assigned to receive either oral S-1 80 mg/m[2]/day (40 mg/m[2] b.i.d.) on days 1 to 21 plus cisplatin 60 mg/m[2] on day 8 every 5 weeks or docetaxel 60 mg/m[2 ]on day 1 plus cisplatin 80 mg/m[2] on day 1 every 3 weeks, both up to 6 cycles. The primary endpoint was overall survival (OS). A non-inferiority study design was employed; the upper confidence interval (CI) limit of the hazard ratio (HR) was <1.322. Secondary endpoints included progression-free survival (PFS), response, safety, and QOL. Subgroup analysis by histology (non-Sq vs Sq) was conducted.

      Results
      From April 2007 through December 2008, 608 patients were randomly assigned to SP (n=303) or DP (n=305) at 66 sites in Japan. Patient demographics were well balanced between the two groups. Non-Sq and Sq patients in SP/DP arm was 251/247 and 50/48 respectively. Two interim analyses were preplanned. At the final analysis, a total of 480 deaths had occurred. The primary endpoint was met. OS in the SP arm was non-inferior to that in the DP arm (median survival, 16.1 vs. 17.1 months, respectively; HR=1.013; 96.4% confidence interval, 0.837-1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. The rates of febrile neutropenia (7.4% vs. 1.0%), grade 3/4 neutropenia (73.4% vs. 22.9%), grade 3/4 infection (14.5% vs. 5.3%), and grade 1/2 alopecia (59.3% vs. 12.3%) were significantly lower in the SP arm than in the DP arm. In terms of physical functioning and global functioning on the EORTC QLQ-C30 and lung cancer module (LC-13), QOL was better in the SP arm (repeated measures ANOVA: p<0.01). Subgroup analysis by histology revealed that the median OS of non-Sq and Sq patients in SP/DP group was 17.4/19.1 months and 12.3/11.7 months respectively, of which hazard ratio was 0.973 (95% CI, 0.797-1.187) and 1.239 (95% CI, 0.819-1.874). Interaction P value was 0.3004.

      Conclusion
      S-1 plus cisplatin is a standard first-line chemotherapeutic regimen for advanced NSCLC both non-Sq and Sq histology. Favorable toxicity profile of the SP regimen and encouraging outcome in patients with non-Sq prompted us to conduct a prospective study of SP plus BEV and maintenance S-1 BEV for non-SQ currently underway.

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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): S. Kudoh

      • 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.