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H.S. Shim



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    MO07 - NSCLC - Targeted Therapies II (ID 114)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO07.08 - The frequency and impact of ROS1-rearrangement on clinical outcomes in never-smokers with lung adenocarcinoma (ID 1253)

      16:55 - 17:00  |  Author(s): H.S. Shim

      • Abstract
      • Presentation
      • Slides

      Background
      To determine the frequency and predictive impact of ROS1-rearrangements on treatment outcomes in never-smoker patients with lung adenocarcinoma.

      Methods
      We concurrently analyzed ROS1- and ALK- rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never-smokers with lung adenocarcinoma. ROS1- and ALK- rearrangements were identified by fluorescent in situ hybridization.

      Results
      Of 208 tumors screened, seven (3.4%) were ROS1-rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase polymerase chain reaction. The frequency of ROS1-rearrangement was 5.7% (6/105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1-rearrangement had a higher objective response rate (ORR; 60.0 vs. 8.5%; P=0.01) and a longer median progression-free survival (PFS; not reached vs. 3.3 months; P=0.008) to pemetrexed than those without ROS1/ALK-rearrangement. The PFS to EGFR-TKIs in patients harboring ROS1-rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 vs. 7.8 months; P=0.01).

      Conclusion
      The frequency of ROS1-rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1-rearrangement is a druggable target in East-Asian never-smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1-rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-001 - Transglutaminase 2 can be predictive of epidermal growth factor receptor tyrosine kinase inhibitor efficacy and cytotoxic chemotherapy success in non-small cell lung cancer (ID 96)

      09:30 - 09:30  |  Author(s): H.S. Shim

      • Abstract

      Background
      Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and the constitutive activation of NF-κB, a pro-inflammatory transcription factor. We investigated the association of the EGFR-TKI or cytotoxic chemotherapy clinical efficacy with transglutaminase 2 and NF-ĸB expression in non-small cell lung cancer (NSCLC).

      Methods
      TG2 and NF-ĸB expression was immunohistochemically studied in 120 patients with NSCLC who received an operation. Kaplan-Meier survival analysis and Cox regression analysis were used to estimate the effect of TG2 and NF-ĸB expression on chemotherapy clinical efficacy.

      Results
      Median age of patients was 64 years (41–82). There were 102 (85%) cases of adenocarcinoma and 18 patients (15%) had other histologies. Eight patients received adjuvant chemotherapy, 29 received platinum-based doublet chemotherapy and another 29 patients received EGFR-TKI. Smoking status was as follows: 25 current, 16 former and 79 never. There were 55 patients with an EGFR mutation. TG2 median value was 50 (0 to 300) and NF-kB median value was 20 (0 to 240). Response to platinum-based doublet was as follows: Overall response rate (ORR) was 13.8% and disease control rate (DCR) was 69% (Complete response (CR) 0%, partial response (PR) 13.8%, stable disease (SD) 55.2% and progressive disease (PD) 24.1%). Responses to EGFR-TKI was as follows: ORR was 24.1% and DCR was 58.6% (CR 3.4%, PR 20.7%, SD 34.5% and PD 34.5%). Among the 88 patients who received adjuvant chemotherapy, disease-free survival (DFS) did not differ between the low and high TG2 groups. Among patients (n=29) who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was significantly longer in the low TG2 group when compared with the high TG2 group (34.0 versus 15.0 months, p = 0.003). Among those who received EGFR-TKI (n=29) (first line 7, second line 18, third line 3, fourth line 1), PFS was significantly longer in the low TG2 group when compared with high TG 2 group (11.0 versus 2.0 months, p = 0.013). In patients with EGFR wild-type mutations treated with EGFR-TKI, progression free survival was longer in patients with low TG2 expression (9.0 vs 2.0 months, p=0.013).

      Conclusion
      This study suggests that TG2 expression can be predictive of success of cytotoxic chemotherapy and EGFR-TKI for patients with non-small cell lung cancer, particularly in patients with EGFR wild-type mutations.