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S. Ren



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-008 - Clinical Significance of Hyperpigmentation due to Pemetrexed Treatment in Advanced Non-Squamous Non-small cell lung cancer in China (ID 719)

      09:30 - 09:30  |  Author(s): S. Ren

      • Abstract

      Background
      Previous publications have demonstrated the efficacy of pemetrexed (PEM) as first-line, second-line and maintenance therapy in advanced non-small cell lung cancer (NSCLC). A recent study found skin toxicities compromised continuation of PEM treatment. The purpose of this study is to investigate the clinical significance of hyperpigmentation (HP) in advanced non-squamous (NS) NSCLC receiving PEM-based therapy in China.

      Methods
      Medical records of patients with advanced NS NSCLC who received PEM-based treatment in our hospital were retrospectively studied. Chi-square test, Pearson’s test as well as Kaplan-Meier method and Cox Proportional Hazards model were performed for statistical analysis.

      Results
      A total of 101 patients were collected with a median age of 58 years old. Among them, 53 (52.5%) were female and 65 (64.4%) were nonsmokers. 52 (51.5%) patients received first-line treatment. Presence of HP was associated with better ORR (22% vs 7.1%, p=0.043), higher DCR (84.7% vs 54.8%, p=0.001), and had longer PFS (186 days versus 96 days, p<0.0001). There were no significant differences according to grade of HP in ORR, DCR and PFS. There was a higher incidence of hyperpigmentation in patients who received first-line treatment (73.1%% vs 42.9%, p=0.023) and doublet chemotherapy (43.1% vs 74.0%, p=0.002). However,multivariate analysis demonstrated HP was not an independent factor for better clinical outcomes (vs absence, Hazard Ratio [HR] 0.417, 95% Confidential Interval [CI] 0.255-0.690, p=0.493).

      Conclusion
      HP due to PEM is frequent in advanced NS NSCLC receiving PEM. It might be a predictive factor for better clinical outcomes in Pemetrexed-treated advanced NS NSCLC in China.

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    P1.18 - Poster Session 1 - Pathology (ID 175)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P1.18-001 - The prevalence and clinicopathologic feature of ALK, ROS1 and RET fusions in East Asian patients with lung adenocarcinoma (ID 49)

      09:30 - 09:30  |  Author(s): S. Ren

      • Abstract

      Background
      ALK, ROS1 and RET fusions have been demonstrated as oncogenic drivers in lung cancer. Of these, ALK fusions were shown to occur more frequently in patients with mucinous adenocarcinoma or solid histology with signet-ring cells. The association of ROS1 and RET fusions with the adenocarcinoma component remains unclear. We conducted this study to determine the prevalence and clinicopathologic characteristics of ALK, ROS1 and RET fusions in East Asian patients with lung adenocarcinoma, and investigate the association of the above-mentioned gene fusions with histological subtype of adenocarcinoma according to the IASLC/ATS/ERS Classification.

      Methods
      We screened 620 Chinese patients with histologically confirmed lung adenocarcinoma for ALK, ROS1 and RET fusions using multiplex RT-PCR and validated all fusion-positive patients using direct sequencing. The patterns of gene fusions screened in this study contained EML4-ALK (17 variants), CD74-ROS1, SLC34A2-ROS1, SDC4-ROS1, EZR-ROS1, TPM3-ROS1, LRIG3-ROS1, GOPC-ROS1, KIF5B-RET, CCDC6-RET and NCOA4-RET. The association of ALK, ROS1 and RET fusions with different subtype of adenocarcinoma were analyzed in 331 patients. The data for remaining 289 patients are being analyzed. All patients enrolled in this study were followed up for survival.

      Results
      Of the 620 patients with adenocarcinoma screened, 472 (76.1%) patients were never/light smokers (<10 pack-years), and 148 (23.9%) were smokers (≥10 pack-years), with the median age of 59 (range, 27-82) years; 348 patients were female, accounting for 56.1%. Patients with stage I, II, III, or IV disease accounted for 56.6%, 8.7%, 27.1% and 7.6%, respectively. The prevalence of ALK, ROS1 and RET fusions in this study was 8.1% (50/620), 3.5% (22/620) and 1.9% (12/620), respectively. Among the 331 patients diagnosed by the IASLC/ATS/ERS Classification, 15 patients were identified positive for EML4-ALK fusions (including 8 solid, 2 acinar, 2 colloid, 1 lepidic, 1 papillary and 1 micropapillary predominant), 7 patients were positive for ROS1 fusions (including 2 acinar, 2 papillary, 1 lepidic, 1 solid and 1 mucinous predominant), and 4 patients were positive for RET fusions (including 2 acinar, 1 micropapillary and 1 solid predominant).

      Conclusion
      These fusion-positive patients may have unique pathologic feature compared with fusion-negative patients. EML4-ALK fusions were shown to occur in solid predominant adenocarcinoma with a higher frequency in this study. The association of ALK, ROS1 and RET fusions with the subtype of lung adenocarcinoma and the data of survival are being analyzed in all patients and will be presented at the conference.

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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-014 - Quantitative test of mutant EGFR and its effect on efficacy of EGFR TKI in advanced NSCLC (ID 1327)

      09:30 - 09:30  |  Author(s): S. Ren

      • Abstract

      Background
      It is reported that abundance of EGFR mutations is related with efficacy of EGFR TKI in advanced NSCLC patients with mutant EGFR. This study was designed to investigate influence of EGFR mutations and their abundance on efficacy of EGFR TKI by a quantitative method.

      Methods
      190 NSCLC treated with EGFR TKI and available tissue for EGFR mutations were enrolled into the study; 113 were FFPE specimen, and 62 were fresh tissue. EGFR mutation was detected with the kit of AmoyDx ARMS and percentage of mutant EGFR was tested with the method of an Allele Specific PCR with Competitive Blocker (ASB-PCR). In this assay, copies of EGFR mutants were calibrated by standard curve, and the mutation rates were estimated through normalizing by copies of a conserved sequence in EGFR exon2. The relationship between abundance of EGFR mutations and efficacy of EGFR TKI was analyzed.

      Results
      Of 190 samples, 15 were censored due to EGFR exon2 copies less than 100; finally, 175 enrolled into data analysis. Mutant percentage less than 0.1% was defined as wild-type, 0.1%~2% as low abundance, 2%~20% as moderate abundance, and more than 20% as high abundance. The mutant rate was 56.6% and 62.3% by using AmoyDx ARMS and ASB-PCR methods, respectively. The accordance rate of EGFR mutations was 89.7% by two methods. Of 175 samples, 20, 27 and 62 harbored low, moderate and high abundances of mutant EGFR, respectively; 66 were wild-type EGFR. Median progress free survival (mPFS) was 4.9 (95% CI, 3.4 to 6.4), 8.3 (95% CI, 3.3 to 13.3) and 16.0 months (95% CI, 10.4 to 21.7) in patients with low, moderate and high abundances of mutant EGFR (p =0.012). The mPFS of low abundance was not longer than that of those patients with wild-type EGFR (2.0 months, 95% CI, 0.2 to 4.1; p=0.261). Objective response rate (ORR) was 67.7%, 44.4%, 25.0% and 19.7%, and disease control rate (DCR) was 90.3%, 81.5%, 55.0% and 45.5% in patients with high, moderate, low abundance and wild-type EGFR, respectively (p<0.001). But ORR and DCR were no difference between low abundance and WT groups (p=0.754; p=0.610, respectively).

      Conclusion
      The abundance of EGFR mutations could affect the efficacy of EGFR-TKI, and quantitation of mutant EGFR could better predict for efficacy of EGFR TKI in advanced NSCLC.