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X. Hao



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    P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.11-038 - The significance of ALK rearrangement in selected advanced non-small cell lung cancer: ALK expression provides insights into ALK target therapy (ID 2757)

      09:30 - 09:30  |  Author(s): X. Hao

      • Abstract

      Background
      ALK rearrangements are detected in 3%~7% in unselected non-small cell lung cancer (NSCLC) and accurate determination of ALK rearrangements are the key importance to screen appropriate candidates for ALK inhibitor therapy. Previous studies showed that IHC could be a promising prescreening method. However, the correlation between IHC results and clinical outcomes had not been confirmed. This study aimed to elucidate clinical significance of ALK rearrangement in selected advanced NSCLC patients and evaluate a possible association between ALK expression and clinical outcomes in ALK positive crizotinib-treated patients.

      Methods
      ALK status was assessed by FISH, immunohistochemistry (IHC) and quantitative RT-PCR(qRT-PCR) in 173 selected advanced NSCLC patients who were aiming at undergoing ALK screening for crizotinib therapy. Clinicopathologic data, genotype status and survival outcomes were analyzed. In addtion, we correlated ALK expression with clinical outcomes in crizotinb treated patients including two patients with concurrent ALK rearrangement and EGFR mutation.

      Results
      ALK positive detection rate was 35.5% (59/166), 36.3% (61/168), 27.9% (34/122) by FISH, IHC and qRT-PCR, respectively. Among the 166 advanced NSCLC patients who were successfully underwent ALK screening by FISH, 20 patients with EGFR mutation, 87 patients with wild type status and 2 (3.4%, 2/59) patients with concurrent ALK rearrangement and EGFR mutation. Of the 59 patients with FISH-positive ALK rearrangement, 45 received crizotinib in the phase II clinical trial (PROFILE 1005), 8 were enrolled in the phase III clinical trial (PROFILE 1014) and 6 did not participate in any clinical trial. ALK-positive patients have distinct clinicopathological features. ALK FISH-positive and crizotinib-treated patients (PROFILE 1005) had a median progression-free survival (PFS) of 7.6 months and longer overall survival (OS) compared with crizotinib-naïve (P<0.0001) or wild type cohorts (P=0.0138), but there was no significant difference in OS compared with EGFR mutation patients(P=0.8959). ALK positive and negative patients divided by qRT-PCR in the ALK FISH crizotinib-treated patients had no different in clinical outcomes. ALK expression was not associated with PFS (P=0.792) and OS (P=0.325). However, when used IHC expression as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P=0.026). The two patients with concurrent EGFR mutation and ALK rearrangement had difference in ALK expression, response to TKIs and crizotinib, and overall survival.

      Conclusion
      In the era of ALK-targeted inhibitors, enriching NSCLC patients according to clinicopathologic characteristics could highly improve ALK detection rate for molecular target therapy. IHC could be a supplementary method to provide more clues for clinical trial design and therapeutic strategies for NSCLC patients who harbor ALK rearrangement including patients with double genetic aberration of ALK and EGFR.

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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-043 - Analysis of clinicopathological features for Chinese patients with advanced non-small cell lung cancer harboring EML4-ALK fusion genes (ID 2968)

      09:30 - 09:30  |  Author(s): X. Hao

      • Abstract

      Background
      The echinoderm microtubule-associated protein like-4—anaplastic lymphoma kinase (EML4--ALK) fusion oncogene defines a novel molecular subset of non-small cell lung cancer (NSCLC). Crizotinib (Xalkori) has been approved for patients with locally advanced or metastatic NSCLC that is ALK positive. However, the clinicopathological characteristics of patients with the EML4-ALK gene have not been identified completely.

      Methods
      The clinicopathological characteristics of 200 Chinese patients with advanced NSCLC were analyzed retrospectively．Clinical factors including age, sex, smoking history, pathological type, biopsy method, site of biopsy and interval between biopsy and the identification of EML4-ALK fusions and the status of epidermal growth factor receptor (EGFR) mutation were analyzed to investigate possible correlations with EML4-ALK fusions.

      Results
      Among the 200 patients with NSCLC enrolled, 56 (28.0%) harbored the EML4-ALK gene in this retrospective study. EML4-ALK fusions could not be detected in 22 of 200 patients (11.0%) because of insufficient tissue. The median age was 53 as a whole. The median ages of ALK positive and negative groups were 48 and 55 years, respectively. Patients with the EML4-ALK gene were significantly younger than patients without EML4-ALK (p＜0.001). The detection rate of EML4-ALK rearrangement in patients with tumor or metastatic lymph nodes resection was significantly higher than patients with needle biopsy(p=0.003). If the interval between biopsy and the identification of EML4-ALK fusions was less than 48 months, the detection rate of EML4-ALK rearrangement was significantly higher compared with the interval more than 48months(p=0.020). Among the 200 patients, 103(51.5%) patients had received EGFR mutation detection. Only 1 case harbored both EML4-ALK rearrangement and EGFR mutations. The incidence of EML4-ALK rearrangement in patients with EGFR wide type（42.5%,37/87）was significantly higher than EGFR mutant type（6.3%,1/16）. No significant difference in the distribution of sex, smoking history, pathological type, and site of biopsy(lung tumor compared with metastatic lymph nodes) was observed between ALK positive and negative groups (p = 0.140, 0.103, 0.438 and 0.217, respectively).

      Comparisons of patient characteristics according to genotype
      EML4-ALK gene
      Characteristics Total,n Positive,n Negative,n P value
      56 122
      Age(years)
      Median 53 48 55 ＜0.001
      Range 25-76 25-74 27-76
      Sex
      Male 78 20 58 0.140
      Female 100 36 64
      Smoking history
      Never/light smokers 143 49 94 0.103
      Smokers 35 7 28
      Pathological type
      Adenocarcinoma 161 52 109 0.438
      Non- adenocarcinoma 17 4 13
      Biopsy method
      Tumor and metastatic lymph nodes resection 158 49 109 0.003
      Needle biopsy 20 7 13
      Site of biopsy
      Lung tumor 99 27 72 0.217[$]
      Metastatic lymph nodes 72 26 46
      Pleura 2 1 1
      Others 5 2 3
      Interval between biopsy and the identification of EML4-ALK fusions (months)
      ≤48 167 55 112 0.020
      ＞48 11 1 10
      EGFR mutation(n=103)
      Mutant type 16 1 15 0.005
      Wide type 87 37 50
      $:lung tumor compared with lymph nodes

      Conclusion
      We identified younger age and EGFR wide type as clinicopathological features of patients with advanced NSCLC harboring EML4-ALK fusion genes. The detection rate of EML4-ALK rearrangement was significantly higher in patients with tumor or metastatic lymph nodes resection and the interval less than 48 months between biopsy and the identification of EML4-ALK fusions.

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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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      P3.11-043 - Survival of patients with advanced lung adenocarcinoma before and after approved use of Gefitinib in China: a comparative clinical study in a single center (ID 2973)

      09:30 - 09:30  |  Author(s): X. Hao

      • Abstract

      Background
      Since approved use of Gefitinib in March 2005 in China, more patients with lung cancer, especially those with lung adenocarcinoma, have chosen it for treatment. It is of clinical significance to compare survival of lung adenocarcinoma patients who received Gefitinib treatment after March 2005 and that of those who did not receive it so as to provide clinical clues for selection of Gefitinib in Chinese lung adenocarcinoma patients.

      Methods
      Clinical data of 558 patients with advanced lung adenocarcinoma who received palliative chemotherapy from January 2002 throughout December 2010 were reviewed retrospectively. According to the matched-pair case-control study design, 255 patients who only received palliative chemotherapyand 255 patients who received Gefitinib treatment after approved use of Gefitinib were stringently matched by age, sex and smoking history and finally enrolled in this study. Clinical factors including age, sex, smoking history, Eastern Cooperative Oncology Group performance status (ECOG PS), tumor stage, organ metastasis and the number of prior cytotoxic chemotherapies were analyzed to determine their correlations with OS.

      Results
      The median survival time (MST) of the 510 enrolled patients with advanced lung adenocarcinoma was 22.8 months. MST of the patients who received Gefitinib treatment was significantly longer than that of the patients without (33.5 months vs. 14.1 months, p<0.001). OS in patients who received Gefitinib treatment was significantly longer than that in patients without receiving Gefitinib treatment in almost all clinical factor-based subgroups, including age, sex ,smoking history, ECOG PS 0-1, tumor stage, the presence or absence of lung, pleural, bone, brain, adrenal gland and liver metastasis, and the number of prior cytotoxic chemotherapies (all p<0.001), except in ECOG PS ≥2 subgroup.

      Conclusion
      Gefitinib treatment significantly improved the survival of patients with advanced lung adenocarcinoma in China.