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A. Kubo



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    O18 - Cancer Control and Epidemiology II (ID 133)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      O18.02 - Impacts of environmental tobacco smoke on EGFR mutations and ALK rearrangements in never smokers with non-small cell lung cancer: Analyses on a prospective multinational ETS registry (ID 1255)

      10:30 - 12:00  |  Author(s): A. Kubo

      • Abstract
      • Presentation
      • Slides

      Background
      EGFR and ALK are important driver mutations in never smokers. While we reported the significant association of increased environmental tobacco smoke (ETS) with EGFR mutations in Japanese cohort (Kawaguchi, Clin Cancer Res, 2011), it has not been fully understood in other ethnicities and also the correlation of ETS with ALK has not been reported yet. In this study, we evaluated the association of ETS with the prevalence of EGFR mutations and ALK translocations in various ethnicities including East-Asia (Japan, Korea, China, and Singapore) and the USA.

      Methods
      ETS exposure on never smokers with non-small cell lung cancer (NSCLC) was evaluated using the standardized questionnaire including exposure period, place, and duration. Cumulative dose of ETS (CETS) was defined as a sum of the number of the exposure years in childhood/ adulthood and at home/ workplace, and was treated as a continuous variable or quintile. EGFR mutations and ALK rearrangements were tested by PCR-based detection and fluorescence in situ hybridization, respectively. Multivariate analyses were done using the generalized linear mixed model (GLIMMIX procedure, SAS v9.3).

      Results
      From March 2008 to December 2012, 498 never smokers with NSCLC were registered with the following patient characteristics: ethnicity (nationality) of Asian/ Caucasian/ others, 425 (Japanese 250, Korean 102, Chinese 46, others 2)/ 48/ 25; male/ female, 114/ 384; age <65/ >=65, 286/ 212; histology of adenocarcinoma/ BAC/ squamous cell carcinoma/ adenosquamous cell carcinoma/ other NSCLC, 459/ 12/ 13/ 5/ 9; frequency (%) of CETS < median CETS (40 years) in Japanese/ Korean/ Chinese/ Caucasian, 32.8/ 44.1/ 71.7/ 83.3. EGFR status was wild type 43.6%, exon 19 deletion 25.3%, L858R 21.5% and other mutations 9.6%. ALK status was wild type 52.0%, rearranged 10.6% and unknown 37.3%. Average CETS (years) of NS with EGFR (+), ALK (+) and wild type tumors were 45.4, 26.9 and 37.7, respectively. In multivariate generalized linear mixed model, incidence of activating EGFR mutations, not ALK rearrangements, was significantly associated with the increment of CETS in female, not in male gender. Odds ratios (OR) for EGFR mutations in female (n=384) were 1.084 (95% CI, 1.003-1.171; p=0.0422) for each increment of 10 years in CETS while OR in male (n=114) were not significant (OR 0.890; 95% CI, 0.725-1.093; p=0.2627). OR for ALK rearrangements in female (n=238) and those in male gender (n=74) were 0.930 (0.791-1.094; p=0.3814) and 0.854 (0.620-1.178; p=0.3319).

      Conclusion
      Increased ETS exposure was closely associated with EGFR mutations in never smokers with female gender and NSCLC in the expanded multinational cohort. However, the association of ETS and ALK rearrangements in never smokers with NSCLC was not significant.

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    P1.24 - Poster Session 1 - Clinical Care (ID 146)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P1.24-019 - Therapeutic and preventive effects of aprepitant for chemotherapy-induced nausea and vomiting in Japanese patients with thoracic malignancies (ID 1510)

      09:30 - 16:30  |  Author(s): A. Kubo

      • Abstract

      Background
      Neurokinin-1 receptor antagonist (NK1RA) in addition to 5-hydroxytryptamine receptor antagonists (5HT3RA) and dexamethasone (Dex) is recommended for chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC). It had been also reported that 40-60% of patients receiving HEC had not experienced significant nausea and/or vomiting before NK1RA became available. In 2010 NK1RA aprepitant was introduced for CINV prophylaxis in Japan. However, what proportion of patients receiving emetogenic chemotherapy need NK1RA, and whether all patients undergoing HEC truly need NK1RA remain unknown. Increasing medical costs due to uniform use of NK1RA is another concern. The primary objective of this study is the prevalence of patients who require aprepitant. Therapeutic and preventive effects of aprepitant on CINV induced by HEC or moderately emetogenic chemotherapy (MEC), and quality of life (QOL) regarding CINV are secondary objectives. We conducted this single-institute study before fully introducing aprepitant into clinical practice in our institute.

      Methods
      From July 2011 to January 2013, 96 consecutive patients receiving HEC or MEC, with age ≥ 20, able to use Japanese language, and with written informed consent, were enrolled onto the study, and 77 patients were analyzed who received ≥ 2 courses in the same chemotherapy regimen. 5-HT3RA and Dex were administered to prevent CINV. Aprepitant was administered to treat CINV in the first course when CINV occurred, or administered to prevent CINV in the second course. All patients who experienced CINV in the first course received prophylactic aprepitant from the second course. QOL regarding CINV was assessed by Functional Living Index of Emesis (FLIE). Numerical rating scale (NRS) was used to assess the severity of nausea. This study was approved by the Institutional Review Board of Aichi Medical University.

      Results
      Patient characteristics were: median age (range), 67 (38-85); gender (male/female), 64/13; cancer type (lung cancer/thymic tumor/other), 72/3/2; chemotherapy regimen (HEC/MEC), 28/49. Aprepitant was not administered in 57% and 88% of patient who received HEC and MEC, respectively. In patients treated with aprepitant (n=18), therapeutic use of aprepitant after CINV occurred (n=9) decreased average NRS for nausea and average frequency of vomiting per day from 7.44 to 5.44 (p=0.10), and 2.11 to 0.11 (p=0.03), respectively. Prophylactic use of aprepitant in the second course (n=18) increased the proportion of patients with no significant nausea from 6% (first course) to 50% (second course, p=0.007), and those with no vomiting from 33% to 89% (p=0.002). In contrast, in patients who did not require aprepitant (n=59), proportion of patients with no significant nausea and those with no vomiting did not change during the 2 courses (76% to 76% [p=1.00] and 92% to 92% [p=1.00], respectively). In patients who required aprepitant, aprepitant use significantly improved FLIE scores in the second course while these did not change in patients who did not require aprepitant.

      Conclusion
      More than half of patients receiving HEC and 88% of patients receiving MEC did not require aprepitant. Aprepitant showed significant therapeutic and preventive effects on CINV in patients who truly need it.