Virtual Library

Start Your Search

C. Zhou



Author of

  • +

    JCHS - Joint IASLC - Chinese Society for Clinical Oncology - Chinese Alliance Against Lung Cancer Session (ID 239)

    • Event: WCLC 2015
    • Type: Joint Chinese/ English Session
    • Track: Other
    • Presentations: 1
    • +

      JCHS.09 - Circulating Tumor Cells and Evaluation of Targeted Therapy Effect in EGFR Mutation/ALK Translocation Metastatic Non-Small Cell Lung Cancer (ID 3526)

      09:35 - 09:45  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Background:
      Targeted therapies have considerably improved the prognosis of patients with non-small cell lung cancer (NSCLC).Although not precision enough, RESIST criteria was still the most often used response assessment method to reflecting the clinical benefits. We propose a non-invasive, folate receptor (FR)–based circulating tumor cell (CTC) detection approach to interpret treatment response of targeted therapy between baseline and follow-up CTC values in EGFR mutation/ALK translocation advanced NSCLC.

      Methods:
      One hundred and thirty eight patients were enrolled in our study. Peripheral blood was analyzed for CTCs enumeration on negative enrichment by immunomagnetic beads. Changes of CTCs levels were correlated with radiological response. Sequential analyses were conducted to monitor CTC signals during therapy and correlate radiological effects with treatment outcome.

      Results:
      CTCs were detected (≥8.7CTC) in 84.8% of patients. Pretreatment and pro-treatment blood samples from all 118 EGFR-mutant (19deltion:56, L858R:57, G719x:3, L861Q:1, 19 deletion + L858R:1), 14 ALK translocation lung cancer patients and 6 EGFR wild type patients were collected. Of 89 eligible and evaluable patients, baseline CTC counts were not associated with response to treatment by RECIST (P=0.353). There is no difference between exon 19 deletion and L858R of baseline CTC values. (19deletion:19.4 CTCs, L858R:20.9 CTCs,P=0.222) The change of CTCs values increased correlation with radiological response (P=0.042) after treatment of targeted therapy. There is no significant difference between exon 19 deletion and L858R of CTCs values pre and pro EGFR-TKI treatment.(3.32 vs.12.1, P=0.783)

      Conclusion:
      This study confirms the predictive significance of CTCs in patients with EGFR mutation/ALK translocation NSCLC receiving targeted therapy. The change of CTCs value correlated significantly with radiological response. This strategy may enable non-invasive, specific biomarker assessment method for using CTC decreases as an early indication of response to targeted therapy and monitoring in patients undergoing targeted cancer therapies.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
    • +

      MINI05.07 - Circulating Tumor Cells and Evaluation of Targeted Therapy Effect in EGFR Mutation/ALK Translocation Metastatic Non-Small Cell Lung Cancer (ID 1403)

      17:20 - 17:25  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Background:
      Targeted therapies have considerably improved the prognosis of patients with non-small cell lung cancer (NSCLC).Although not precision enough, RESIST criteria was still the most often used response assessment method to reflecting the clinical benefits. We propose a non-invasive, folate receptor (FR)–based circulating tumor cell (CTC) detection approach to interpret treatment response of targeted therapy between baseline and follow-up CTC values in EGFR mutation/ALK translocation advanced NSCLC.

      Methods:
      One hundred and thirty eight patients were enrolled in our study. Peripheral blood was analyzed for CTCs enumeration on negative enrichment by immunomagnetic beads. Changes of CTCs levels were correlated with radiological response. Sequential analyses were conducted to monitor CTC signals during therapy and correlate radiological effects with treatment outcome.

      Results:
      CTCs were detected (≥8.7CTC) in 84.8% of patients. Pretreatment and pro-treatment blood samples from all 118 EGFR-mutant (19deltion:56, L858R:57, G719x:3, L861Q:1, 19 deletion + L858R:1), 14 ALK translocation lung cancer patients and 6 EGFR wild type patients were collected. Of 89 eligible and evaluable patients, baseline CTC counts were not associated with response to treatment by RECIST (P=0.353). There is no difference between exon 19 deletion and L858R of baseline CTC values. (19deletion:19.4 CTCs, L858R:20.9 CTCs,P=0.222) The change of CTCs values increased correlation with radiological response (P=0.042) after treatment of targeted therapy. There is no significant difference between exon 19 deletion and L858R of CTCs values pre and pro EGFR-TKI treatment.(3.32 vs.12.1, P=0.783)

      Conclusion:
      This study confirms the predictive significance of CTCs in patients with EGFR mutation/ALK translocation NSCLC receiving targeted therapy. The change of CTCs value correlated significantly with radiological response. This strategy may enable non-invasive, specific biomarker assessment method for using CTC decreases as an early indication of response to targeted therapy and monitoring in patients undergoing targeted cancer therapies.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MINI 10 - ALK and EGFR (ID 105)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
    • +

      MINI10.02 - Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Co-Altered Lung Adenocarcinoma (ID 685)

      16:50 - 16:55  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Background:
      Genetic intratumoral heterogeneity has a profound influence on the selection of clinical treatment strategies and addressing resistance to targeted therapy. The purpose of our study is to explore the potential effect of intratumoral heterogeneity on both the genetic and pathologic characteristics of ALK-rearranged lung adenocarcinoma (LADC).

      Methods:
      We tested ALK fusions and EGFR mutations in 629 LADC patients by using laser capture microdissection (LCM) to capture spatially separated tumor cell subpopulations in various adenocarcinoma subtypes and test for ALK fusions and EGFR mutations in ALK-rearranged, EGFR-mutated, and ALK/EGFR co-altered LADCs in order to compare the oncogenic driver status between different tumor cell subpopulations in the same primary tumor.

      Results:
      Among the 629 patients, 30 (4.8%) had ALK fusions, 364 (57.9%) had EGFR mutations, and 2 had ALK fusions coexisting with EGFR mutations. Intratumoral heterogeneity of ALK fusions was identified in 9 patients by RT-PCR. In the 2 ALK/EGFR co-altered patients, intratumoral genetic heterogeneity was observed both between different growth patterns and within the same growth pattern. Genetic intratumoral heterogeneity of EGFR mutations was also identified in EGFR-mutated NSCLC. ALK fusions were positively associated with a micropapillary pattern (P=0.002) and negatively associated with a lepidic pattern (P=0.008) in a statistically-expanded analysis of 900 individual adenocarcinoma components, although they appeared to be more common in acinar-predominant LADCs in the analysis of 629 patients.

      Conclusion:
      Intratumoral genetic heterogeneity was demonstrated to co-exist with histologic heterogeneity in both single-driver and EGFR/ALK co-altered LADCs. As for the latter, one of the dual altered drivers may be the trunk-driver for the tumor.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MINI 12 - Biomarkers and Lung Nodule Management (ID 109)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Screening and Early Detection
    • Presentations: 2
    • +

      MINI12.03 - Comprehensive Analysis of MicroRNA Expression Patterns in Lung Adenocacinoma Presenting with GGNs and Non-Tumorous Tissues (ID 701)

      16:55 - 17:00  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung cancer is the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for about 80% of primary lung cancer cases and approximately two thirds of them are diagnosed at an advanced stage . The poor prognosis of this disease is partially due to the lack of an effective means of early diagnosis. Discovery of an effective and reliable tool for early diagnosis of lung cancer would play a pivotal role in improving the prognosis of patients with lung cancer. Pulmonary ground-glass nodules (GGNs) are increasingly detected in clinical practice. GGNs are related to lung cancer, especially lung adnocacinoma . The subject of how to manage the pulmonary GGNs remains controversial. It is necessary to identify biological markers that can be used to screen high-risk patients in order to allow better lung adenocacinoma presenting with GGNs detection, earlier intervention and increase the likelihood of successful treatment. MicroRNAs are small non-coding RNAs of 18–24 nucleotides, typically excised from 60–110 nucleotide foldback RNA precursor structures . MicroRNAs have drawn significant attention in cancer research after it was linked to oncogenesis and tumor metastasis. Abnormal expression of microRNAs has been found in both haematopoietic and solid tumours by various genome-wide techniques. There is no report about the relationship between microRNA and pulmonary GGNs. It is necessary to identify biological markers that can be used to screen high-risk patients presenting GGNs in order to allow early lung adenocacinoma detection. Our study investigated microRNA expression with the intention to identify a panel of microRNAs for the diagnosis of lung adenocarcinoma presenting with GGNs.

      Methods:
      73 pairs of samples (tumorous and non-tumorous) were surgically resected from lung adnocacinoma patients presenting with GGNs from Shanghai Pulmonary Hospital between May 2012 and June 2014. After obtaining the approval of the patient consent, fresh tissues samples were taken during surgical resection, snap-frozen on dry ice and stored at−80◦C. MicroRNA expression of tumor and non-tumorous tissues was investigated in 3 participants by the next generation sequencing. Then, we analyzed the difference expression microRNA profiles which were identified by second generation sequencing in 73 pairs of lung adenocacinoma presenting with GGNs and adjacent non-tumorous tissues using a quantitative reverse-transcriptase polymerase chain reaction assay (qRT-PCR).

      Results:
      When we compared microRNA expression among lung cancer tissues versus corresponding noncancerous lung tissues via next-generation sequencing, 23 microRNAs had statistical differences in expression between groups. Five microRNAs (hsa−miR−548ar−5p, chr10_7330_star, chr17_10932_star, hsa−miR−148a−3p, hsa−miR−210−3p) exhibited higher expression in the adnocacinoma samples than that in the non-tumorous samples, eighteen microRNAs (hsa−miR−548x−5p, hsa−miR−144−3p, hsa-miR-106a-5p, hsa−miR−548ay−5p, hsa−miR−199a−3p, hsa−miR−378d, hsa−miR−4732−3p, hsa−miR−486−3p, chr7_5517, hsa−miR−1307−5p, chr17_10880, hsa−miR−127−3p, hsa−miR−411−5p, chr1_1402, chr16_10269, hsa−miR−138−5p, hsa−miR−212−3p, hsa−miR−33b−5p) demonstrated lower expression in adnocacinoma samples than that in the non-tumorous samples (P<0.05). Further validated by qRT-PCR, six microRNAs (chr17_10932_star, hsa−miR−148a−3p, hsa−miR−210−3p, chr1_1402, hsa−miR−378d, hsa−miR−138−5p) were statistically differentially expressed in tumorous compared with non-tumorous tissues.

      Conclusion:
      We found a microRNA panel that has considerable clinical value in diagnosing lung adenocacinoma presenting with GGNs. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      MINI12.08 - Validation of Autoantibody Panel for Early Detection of Lung Cancer in Chinese Population (ID 2529)

      17:25 - 17:30  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Background:
      Autoantibodies is an attractive diagnostic approach for early detection of malignant tumors. Our previous studies found a panel of 7 TAAs(p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, GBU4-5) was associated with lung cancer. We performed this large-scale, multi-center clinical trial to validate their ability to aid early diagnosis of lung cancer in Chinese population. Autoantibodies is an attractive diagnostic approach for early detection of malignant tumors. Our previous studies found a panel of 7 TAAs(p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, GBU4-5) was associated with lung cancer. We performed this large-scale, multi-center clinical trial to validate their ability to aid early diagnosis of lung cancer in Chinese population.

      Methods:
      The 7 TAAs were selected from 43 candidate TAAs from our previous studies, which were detected by ELISA in 1915 participants from 5 clinical centers in China. These samples including lung cancer (n = 818), benign lung diseases (n = 386), healthy volunteers (n = 415) and interference group (n = 296). The sensitivity and specificity from 7 TAAs and the traditional cancer biomarkers CEA, NSE and CYFRA21-1 were compared.

      Results:
      The sensitivity and specificity of autoantibody assay were 61% and 90% respectively, which were similar in different subgroups such as age, gender, smoker status and histological type. As for the enrolled patients with lung cancer, the sensitivities were 60% for patients with stage I/II, which were significantly higher than 27% ( p < 0.01)when using the combination of CEA, NSE and CYFRA21-1 to detect patients with lung cancer. While in patients with stage III/IV lung cancer, sensitivities were similar (63% vs. 56%, p > 0.05) and specificity was significantly improved (90% vs 71%, p < 0.01). The specificity was consistent in benign lung diseases and autoimmune diseases(interference group) and were 90% and 94% respectively and a concentration decrease of 7 TAAs were also observed after tumor resection.

      Conclusion:
      This study suggest that the 7 TAAs autoantibody panel can be used to aid diagnosis of lung cancer, and show a significantly improving sensitivity in patients with early stage lung cancer when comparing with the combination of CEA, NSE and CYFRA21-1.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MINI 13 - Genetic Alterations and Testing (ID 120)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
    • +

      MINI13.12 - The Abundance of EGFR Mutations Could Be More Better Predictor for EGFR-TKI Therapy in Advanced Non-Small Cell Lung Cancer (ID 1481)

      11:50 - 11:55  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Background:
      Incresing data show advanced non-small cell lung cancer (NSCLC) patients with EGFR activating mutant have discrepant response to EGFR-TKI. The abundance of EGFR mutations may be a powerful explanation for the uneven clinical benefit. This study was designed to investigate the influence of EGFR mutant abundance on efficacy of EGFR-TKI by a quantitative method.

      Methods:
      201 NSCLC patients treated with EGFR-TKI with available tissue samples for EGFR mutation test were enrolled into the study. EGFR common mutations were detected by amplification refractory mutation system (ARMS) and percentage of mutant EGFR was tested with the method of an Allele Specific Quantitative PCR with Competitive Blocker (ASB-qPCR). In this assay, the copies of all mutations and EGFR locus were calculated by standard curve respectively. The cutoff values were obtained by the receiver operating characteristics (ROC) curve in training set. Further, the cutoff values were confirmed in validation set and the whole population. The relationship between the abundance of EGFR mutations and efficacy of EGFR-TKI was statistically analyzed.

      Results:
      Of the 201 samples, 72 harbored 19DEL mutation, 63 carried L858R mutant, and 66 with wild-type. The cohort was randomly divided into training and validation sets. The cutoff values of 19DEL and L858R mutation abundance were 4.84% and 9.47% determined by ROC curve in training set. 9.7% of patients with 19DEL positive were low abundance (<4.84%, LA group), while 33.3% of L858R-positive patients were LA (<9.47%).High abundance (HA) group, regardless of 19DEL or L858R positive had more longer median progression free survival (PFS) compared with LA and wild-type groups in either validation set or the whole population (15.0 vs 2.0 vs 1.9, 8.0 vs 1.9 vs 1.9; 15.0 vs 4.0 vs 2.0, 12.0 vs 2.0 vs 2.0; p<0.001). COX regression analysis showed that EGFR mutation abundance, together with smoking status, were independent factors of response to EGFR-TKI.

      Conclusion:
      The abundance of EGFR mutation could more precisely predict EGFR-TKI efficacy. NSCLC patients with LA mutation had inferior clinical benefit with EGFR-TKI. The heterogeneity in EGFR mutant abundance partly explain the efficacy discrepancy in patients with 19DEL or L858R positive.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
    • +

      MINI16.05 - Discussant for MINI16.01, MINI16.02, MINI16.03, MINI16.04 (ID 3347)

      17:05 - 17:15  |  Author(s): C. Zhou

      • Abstract
      • Presentation

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

  • +

    MTE 09 - Treatment of Advanced SCLC Including Second Line (Ticketed Session) (ID 61)

    • Event: WCLC 2015
    • Type: Meet the Expert (Ticketed Session)
    • Track: Small Cell Lung Cancer
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/07/2015, 07:00 - 08:00, 708+710+712
    • +

      MTE09.02 - Treatment of Advanced SCLC Including Second Line (ID 1991)

      07:30 - 08:00  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Lung Cancer is the leading cause of cancer-related death[1]. Small-cell lung cancer accounts for about 15-20% of lung cancer[2]. Although SCLC is chemosensitive, majority of SCLC patients develop disease progression soon after the first line therapy and need 2[nd] line therapy. However, over the past decades, most studies have failed and there is no substantial progress in second-line therapy for SCLC[3]. Topotecan remains 2[nd] line therapy for SCLC patients with sensitive relapse. 1. Targeted therapy Almost all of the studies focused on the molecular targeted therapy for second-line treatment of SCLC were failed. However, in a recent randomized phase II trial (CALGB 30504) of chemotherapy with or without maintenance sunitinib for untreated extensive-stage SCLC, the primary end point [progression-free survival (PFS)] was met for maintenance sunitinib than placebo [median PFS: 3.7 vs 2.1 months; hazard ratio (HR), 1.62; 95% confidence interval (CI), 1.02 to 2.60; P = 0.02]. Overall survival (OS) in maintenance group was also better than in placebo (median OS: 9.0 vs 6.9 months; HR, 1.28; 95% CI, 0.79 to 2.10; P = 0.16). This result suggested that maintenance sunitinib was safe and improved PFS in extensive-stage SCLC[4]. 2. Topotecan Single-agent chemotherapy such as topotecan, paclitaxel, docetaxel, irinotecan, gemcitabine, ifosfamide, vinorelbine and temozolomide have been studied in 2[nd] line therapy of SCLC. But single agent topotecan is the only second-line therapy approved by the U.S. Food and Drug Administration for the treatment of relapsed SCLC. Both oral and intravenious topotecan could significantly improve PFS and OS compared with placebo. Compared with cyclophosphamide, doxorubicin, and vincristine (CAV) regimen in relapsed SCLC patients (n = 211), topotecan produced comparable efficacy but poorer quality of life [5]. Toxicity of topotecan could not be tolerated in many patients. 3. Amrubicin Anthracyclines, including doxorubicin, liposomal doxorubicin, epirubicin, mitoxantrone, have been studied in 2[nd] line therapy of SCLC. Tumor response rate ranged from 0% to 20%. Amrubicin, a third-generation anthracycline and potent topoisomerase II inhibitor, has shown promising activity in SCLC. In ACT-1 trial, amrubicin failed to improve OS compared with topotecan but an improvement in OS was noted in patients with refractory disease treated with amrubicin[6]. 4. Immunotherapy Monoclonal antibodies again immune checkpoint inhibitors including ipilimumab, nivolumab and pembrolizumab have been approved as therapy of some solid tumors including melanoma, non-small cell lung cancer (NSCLC), and also studied in SCLC. In the phase Ib KEYNOTE-028 study, SCLC patients who were failure of or inability to receive standard therapy with PD-L1 positivity received pembrolizumab 10 mg/kg, the overall survival rate (ORR) was 35% and safety profiles were consistent with previous studies[7]. Another two trials to explore the efficacy of combination of pembrozulimab and chemotherap/ radiotherapy for extensive-stage SCLC are ongoing (NCT02359019 and NCT02402920). Ipilimumab is a fully human IgG1 cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) monoclonal antibody[8]. In the phase I/II CheckMate-032 study, SCLC patients with progressive disease after > 1 prior line of therapy received nivolumab + ipilimumab or nivolumab monotherapy. The combination or monotherapy showed activity and durable response in SCLC patients who progressed after > 1 prior line of therapy and safety profile was consistent with other tumor types. Unlike NSCLC, second-line therapy has a little progress in SCLC. Second-line treatment for SCLC should be based on the time of recurrence, the reaction and toxicity of first-line chemotherapy, and performance status (PS). A patient’s response to first-line treatment and the duration of the subsequent progression-free period influences the likelihood that a patient will respond to second-line chemotherapy[9]. Tumors that are refractory to first-line chemotherapy or relapse within 60 to 90 days are considered chemoresistant. Tumors whose response to first-line therapy exceeds 60 to 90 days are considered to be chemosensitive and the recommended second-line therapy is the single agent chemotherapy. Topotecan is the optimal choice. Patients in whom response to first-line therapy is maintained for longer than 180 days are likely to benefit from retreatment with prior etoposide/platinum chemotherapy[10]. Immunotherapy in SCLC is widely studied now. References [1] Siegel R, Ma J, Zou Z and Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29. [2] Arcaro A. Targeted therapies for small cell lung cancer: Where do we stand? Crit Rev Oncol Hematol 2015; [3] Spigel DR and Socinski MA. Rationale for chemotherapy, immunotherapy, and checkpoint blockade in SCLC: beyond traditional treatment approaches. J Thorac Oncol 2013;8:587-98. [4] Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, et al. Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance). J Clin Oncol 2015;33:1660-5. [5] von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999;17:658-67. [6] von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol 2014;32:4012-9. [7] A Potential Immune Therapy for Mesothelioma. Cancer Discov 2015; [8] Sharma P and Allison JP. The future of immune checkpoint therapy. Science 2015;348:56-61. [9] Giaccone G, Donadio M, Bonardi G, Testore F and Calciati A. Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy. J Clin Oncol 1988;6:1264-70. [10] Metro G and Cappuzzo F. Emerging drugs for small-cell lung cancer. Expert Opin Emerg Drugs 2009;14:591-606.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    ORAL 01 - Chemotherapy Developments for Lung Cancer (ID 88)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
    • +

      ORAL01.06 - S-1 and Cisplatin versus Docetaxel and Cisplatin in Patients with Untreated Advanced NSCLC: An Randomised, Multicenter, Phase 3 Trial (ID 2734)

      11:39 - 11:50  |  Author(s): C. Zhou

      • Abstract
      • Presentation
      • Slides

      Background:
      Platinum-based doublet chemotherapy is the standard chemotherapeutic regimen for treatment-naïve advanced non-small cell lung cancer (NSCLC). S-1, an oral fluoropyrimidine, combined with carboplatin or cisplatin (CDDP) has demonstrated the non-inferiority to the standard platinum doublet chemotherapy in Japanese NSCLC patients. However, its effectiveness in Chinese NSCLC patients is uncertain. The purpose of this study is to compare the efficacy and safety of these chemotherapeutic regimens in Chinese NSCLC patients.

      Methods:
      We did this randomized controlled study in 21 sites in China. Eligible patients were those aged 18-70 years who was histologically or cytologically confirmed with locally advanced or metastatic NSCLC with no prior radiotherapy, molecular targeted therapy or chemotherapy. Patients were randomized to receive either S-1 orally 80 mg/m[2]/day (40 mg/m[2]2 b.i.d., 80–120 mg/day) with 60 mg/m[2] CDDP on day 8 every 5 weeks (SP) or docetaxel and CDDP (both 75 mg/m[2]) on day 1 every 3 weeks (DP) for up to 6 cycles. Randomisation was stratified by centre, pathological classification, disease stage and gender. The primary endpoint was progression free survival (PFS), analyzed in the full analysis set. The study is registered at ClinicalTrials.jp, number Japic CTI-111479.

      Results:
      Between March 2011 and November 2012, 246 patients from 21 institutions in China were randomly assigned and received SP or DP treatment (124 vs 122) with 18-month follow-up period from the last patient randomized. In the SP and DP group, median PFS was 5.9 and 5.7 months (HR=0.68; 95% CI, 0.48-0.96) respectively, median overall survival was 19.1 and 14.8 months, respectively (HR=0.84; 95% CI, 0.61-1.14). The most common grade 3 or worse adverse events in both treatment groups were neutropenia 3.3% vs 55.1%, leukopenia 1.7% vs 39.0%, and febrile neutropenia 0.8% vs 5.9%, of 121 patients in the SP group and of 118 patients in the DP group, respectively.

      Conclusion:
      The efficacy of SP was non-inferior to DP with a better safety profile. SP would be a new standard first-line chemotherapy regimen for Chinese patients with advanced NSCLC.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
    • +

      P1.01-057 - Gemcitabine plus Platinum versus Other Platinum Doublets in Squamous NSCLC (ID 149)

      09:30 - 09:30  |  Author(s): C. Zhou

      • Abstract

      Background:
      Squamous cell carcinoma is the second most common histologic subtype of non-small-cell lung cancer (NSCLC). Platinum-based doublet chemotherapy regimens remain the basis of front-line systemic treatment. Most studies in NSCLC included all histologic subtypes. Here we present a pooled analysis of gemcitabine in combination with cisplatin or carboplatin, specifically focusing on patients with squamous NSCLC, from three studies for which individual patient data are available. The objective of this analysis was to evaluate the efficacy of first-line gemcitabine plus platinum (GP) compared with other regimens plus platinum (OP).

      Methods:
      This analysis included squamous NSCLC patients from three randomized, open-label, phase III studies of gemcitabine: 1) gemcitabine plus cisplatin versus etoposide plus cisplatin (n=61), 2) gemcitabine plus carboplatin versus paclitaxel plus carboplatin (n=128), and 3) gemcitabine plus cisplatin versus pemetrexed plus cisplatin (n=473). Patients were grouped into the GP subgroup (n=324) or the OP subgroup (n=338). Efficacy measures included overall response rate (ORR), overall survival (OS), and time to disease progression (TTP). Stratified (by study) Cox proportional hazard regression models were used to analyze OS and TTP by random assignment factors to identify potential prognostic factors and explore their predictive value.

      Results:
      Baseline characteristics were similar between the GP and OP groups. Median OS was 9.72 months for GP versus 9.33 months for OP (HR=0.898, p=0.223) (Figure 1). There was a significant difference in median TTP (5.52 months for GP versus 4.73 months for OP; HR=0.792, p=0.008) (Figure 2). ORR was 31.5% for GP, and 27.2% for OP (p=0.229). Cox regression model identified three prognostic factors for OS: Eastern Cooperative Oncology Group performance status, prior radiotherapy, and body mass index. Figure 1. Kaplan–Meier estimates of overall survival Figure 1 Figure 2. Kaplan–Meier estimates of time to disease progressionFigure 2





      Conclusion:
      This pooled analysis further confirmed the efficacy of gemcitabine plus platinum as first-line treatment of squamous NSCLC.

  • +

    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 2
    • +

      P2.01-006 - Continuing EGFR-TKI in Combination with Regional Chemotherapy Beyond RECIST PD for Patients with Advanced EGFR(+) Non-Small Cell Lung Cancer (ID 916)

      09:30 - 09:30  |  Author(s): C. Zhou

      • Abstract

      Background:
      Local therapy showed promising results for the patient who had an oligo-metastasis after acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).Our study is to evaluate the efficacy and safety of continuing EGFR-TKI treatment in combination with regional chemotherapy beyond RECIST progression disease (PD) of EGFR-TKI in advanced patients with EGFR mutation-positive NSCLC.

      Methods:
      Advanced NSCLC patients with EGFR mutation who got a locally progressed in central lung lesion after the treatment of EGFR-TKI were included.Patients received EGFR-TKI continually in combination with super-selectedsystemicarterial infusionwith docetaxel (75 mg/m2) every 21 days until disease progression again or unacceptable side effect.Response to treatment, progression-free survival (PFS) 1 (time to RECIST PD), PFS 2(time to PD if EGFR-TKI was extended beyond RECIST PD) andtreatment-related adverse effects (AEs)were analyzed. Patient-reported outcomes were evaluated inall patients who had completed a baselineassessment and at least one post-baseline assessment based on the QLQ-LC13 scales.

      Results:
      A total of 6 patientswere recruited. Patients had the median age of 54.17 years (range, 40-68 years).Two patients achieved partial responses and four had stable disease. Median PFS1was 11.70±8.97 months. Median PFS2 was 5.36±1.47 months.There was one death (none treatment related). OS data are immature. No unexpected side effects were found in our study.Patients reported significantly greater reductions from baseline in the symptoms of cough, hemoptysis, chest pain and dyspnea (P<0.05 for all comparisons).

      Conclusion:
      Continuing EGFR-TKI in combination with super-selected systemic arterial infusion chemotherapybeyond progression for advanced NSCLC patients with EGFR mutation is feasible and warrent further investigation.

    • +

      P2.01-024 - An ENSURE Extension Study to Evaluate 2<sup>nd</sup> Line Erlotinib and Gemcitabine/Cisplatin Cross-Over Treatment for EGFR-Mutant Chinese NSCLC Patients (ID 1747)

      09:30 - 09:30  |  Author(s): C. Zhou

      • Abstract
      • Slides

      Background:
      ENSURE study shows that 1[st] line treatment with erlotinib provides longer PFS over gemcitabine/cisplatin (GP) for stage IIIB/IV NSCLC patients with EGFR mutations. Cross-over treatments after progression of disease (PD) was allowed in ENSURE study. However, post-study treatments might have significant impact on patient survival or other clinical benefits, which is insufficiently investigated. This trial in an extension of the ENSURE study, intended to evaluate PFS in 2[nd] line progression after cross-over treatments in ENSURE.

      Methods:
      Chinese patients who had PD after 1[st] line treatment in ENSURE were enrolled. Enrolled patients received cross-over treatment as 2[nd] line treatment after 1[st] line PD. The primary endpoint was PFS, defined as the time of randomization in ENSURE to disease progression or death while on 2[nd] line treatment. For patients who had already progressed after 2[nd] line therapy prior to entering this extension study, relevant information would be collected retrospectively. PFS from 1[st] line PD to 2[nd] line PD was also calculated. The study was approved by IRB and all patients signed informed consent. This study was registered in clinicalgrials.gov (NCT02000531). We also retrospectively analyzed the time to 2[nd] line treatment failure (TTF) defined as the time from randomization to discontinuation of 2[nd] line treatment for any reason.

      Results:
      Forty-five patients (21 from erlotinib arm and 24 from GP arm) were enrolled in the final analysis in this ENSURE extension study. Limited recruitment was mainly due to later initiation of this study (from January to December of 2014), many deaths at the beginning of this study, or unwillingness to sign informed consent by some patients. Age, sex, and ECOG at baseline in erlotinib group and GP group were balanced. Among 45 enrolled subjects, 33 (73.3%) subjects completed the study. There was no significant difference in median PFS from the date of randomization in ENSURE study to 2[nd] line PD for both arms 26.3 (95%CI: 19.8 , 34.0 ) months vs 23.4 (95%CI: 17.8, 39.0 ) months, HR=1.26 (95%CI: 0.61, 2.62), p=0.529). For 2[nd] line cross-over treatment, ORR in erlotinib and GP arms was 33.3% (7PR/21) and 66.7% (16PR/24) respectively (p=0.0377). In a retrospective analysis of 175 patients from the whole ENSURE study, 63.2% patients in erlotinib arm (n=87) received 2[nd] line chemotherapy and 86.4% patients in GP arm (n=88) received 2[nd] line targeted therapy. The median TTF in erlotinib and GP arm were 29.4 (95%CI: 24.7, 34.2) and 24.7 (95%CI: 21.9, 28.4) months respectively (HR=0.74(95%CI: 0.47, 1.17), p=0.192).The subgroup analysis (mutation type, ECOG performance status, gender) for TTF between erlotinib and GP arm showed similar trend to the primary analysis.

      Conclusion:
      Despite limitations, both median PFS (in prospective analysis) and TTF (in retrospective analysis) for erlotinib patients were numerically larger than that in GP arm. This first cross-over treatment ENSURE extension study further confirms benefits of erlotinib as standard 1[st] line treatment for EGFR mutant NSCLC. It also supports the importance of 1[st] and 2[nd] line treatment sequence of erlotinib and platinum-based chemotherapy for the treatment of EGFR mutant NSCLC.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P2.06 - Poster Session/ Screening and Early Detection (ID 219)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
    • +

      P2.06-008 - Diagnostic Yield of Autoantibody Panel for Patients with Ground-Glass Nodules (GGNs) or Solid Nodules in Chinese Population (ID 3069)

      09:30 - 09:30  |  Author(s): C. Zhou

      • Abstract

      Background:
      Autoantibodies is an attractive diagnostic approach for early detection of malignant tumors. Our previous studies found a panel of 7 TAAs(p53,PGP9.5,SOX2,GAGE7,GBU4-5,MAGE A1,CAGE) was associated with lung cancer. We performed this large-scale clinical trial to validate their ability to aid early diagnosis of lung adenocarcinoma presenting with GGNs or solid nodules in Chinese population.

      Methods:
      The 7 TAAs were selected from 43 candidate TAAs from our previous studies. These samples including lung adenocarcinoma presenting with GGNs (n = 170) or solid nodules (n = 100) and healthy volunteers (n = 200). The sensitivity and specificity from 7 TAAs and the traditional cancer biomarkers CEA, NSE, and CYFRA21-1 were compared.

      Results:
      The sensitivity and specificity of autoantibody assay were 53% and 91% respectively, which were similar in different subgroups such as age, gender, smoker status and histological type. The sensitivity of autoantibody assay was 50% in lung adenocarcinoma presenting with GGNs. The sensitivity of autoantibody assay was 58% in lung adenocarcinoma presenting with nodules. The results were significantly higher than 27% when using the combination of CEA, NSE, and CYFRA21-1 to detect patients with lung cancer.

      Conclusion:
      Our study suggested that the 7 TAAs autoantibody panel might be helpful to aid diagnosis of lung cancer with GGNs or solid nodule. Large scale trial to validate our finding of patients with GGNs is ongoing in our institute.

  • +

    P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
    • +

      P3.01-052 - Randomized Phase II Individualized Chemotherapy Study Based on BRCA1 and RRM1 Message RNA Level for Advanced NSCLC (BRAVO Study) (ID 2306)

      09:30 - 09:30  |  Author(s): C. Zhou

      • Abstract
      • Slides

      Background:
      We assessed whether BRCA1 and RRM1 message RNA(mRNA) levels could help to select chemotherapy regimen to improve objective response rate in patients with advanced NSCLC.

      Methods:
      Eligible patients were randomly assigned 2:1 according to stratification factors of smoking, gender and histological type. In experimental arm, gemcitabine/cisplatin(GP) were selected if both RRM1 and ERCC1 mRNA levels were low, irinotecan/cisplatin(IP) if RRM1 high and BRCA1 low, gemcitabine/vinorelbine(GN) if RRM1 low and BRCA1 high, and docetaxel(T) if both high. GP was chose in the control arm. The primary end point was objective response rate (ORR). (Registered No. NCT01424709).

      Results:
      121 patients were enrolled and 120 received at least one dose of therapy. The median number of cycles given was four in both arms. In experimental arm, 36 patients treated with GP, 14 with IP, 13 with GN and 17 with T. The ORR and DCR were 33.3% and 79.5% in the experimental arm, which were not significant different from 32.5% (p=0.12) and 87.5%(p=0.18) in the control arm. When patients with both low mRNA levels of RRM1 and ERCC1 were removed, the sub-analysis showed the ORR in the experimental arm was marginally significantly higher than in the control arm (42% vs. 36.3%, p=0.06)). Survival analysis showed similar PFS in the two arms (5.1 vs. 5.3m, p=0.11), while sub-analysis revealed that PFS was marginally significantly longer in the experimental arm (5.7 vs. 5.3m p=0.09). No unexpected side effect happened in both arms.

      Conclusion:
      BRCA1 and RRM1 mRNA levels were potentially used for therapeutic decision making in newly diagnosed patients with advanced NSCLC.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 3
    • +

      P3.04-004 - Utility of Cytology Specimens for ALK Fusion Detected by qRT-PCR in Patients of Advanced Non Small Cell Lung Cancer (ID 2222)

      09:30 - 09:30  |  Author(s): C. Zhou

      • Abstract

      Background:
      Tumor tissue is the essential specimen for anaplastic lymphoma kinase (ALK) rearrangements detection by the methods of fluorescence in situ hybridization assay(FISH) and immunohistochemistry(IHC). However, a lot of patients could just provide cytological samples but not tumor tissue in clinical practice. The aim of this study was to evaluate the feasibility of cytology as an alternative specimen for ALK detection in patients with advanced non small cell lung cancer (NSCLC).

      Methods:
      Advanced NSCLC patients with cytology specimens or tumor tissue who had their ALK fusion status detected by qRT-PCR in Shanghai Pulmonary Hospital, Tongji University were included into this analysis. The efficacy was evaluated in those with ALK fusion and treated with crizotinib.

      Results:
      From December 10[th] 2010 to March 20[th ]2015, 1386 patients entered into this study with 1144 cytology specimens and 242 tumor tissue. Among them, 110 of 1144(9.6%) patients were ALK qRT-PCR positive using cytology specimens to perform detection and 26 of 242(10.7%) patients with tumor tissue were ALK fusion positive. Totally, 69 patients received the treatment of crizotinib. The overall response rate (ORR) of the 50 patients with cytology specimens was 62.0%, which was similar as 52.6% in 19 patients with tissue (p=0.479). Median progression free survival (mPFS) was 8.3 months (95% CI 6.91-9.75) in the cytology specimens group, which was also similar as 5.2 months (95% CI 2.58-7.82) (p=0.604) in the tissue group.

      Conclusion:
      Cytology specimens showed a high feasibility to perform ALK fusion status detection by qRT-PCR and a similar response to ALK inhibitor as tissue specimens, which might be regarded as alternative specimens for ALK detection in patients of advanced NSCLC.

    • +

      P3.04-010 - EML4-ALK Fusion Detected by qRT-PCR Confers Similar Response to Crizotinib as Detected by FISH in Patients with Advanced NSCLC (ID 2338)

      09:30 - 09:30  |  Author(s): C. Zhou

      • Abstract
      • Slides

      Background:
      Quantitative reverse transcriptase polymerase chain reaction assay (qRT-PCR) has been proved to have high sensitivity and specificity to detect anaplastic lymphoma kinase (ALK) rearrangements. The aim of this study was to investigate the response to crizotinib in patients of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements detected by qRT-PCR.

      Methods:
      Patients with advanced NSCLC who had their ALK rearrangement status detected by qRT-PCR were included in this analysis. The utility of qRT-PCR and fluorescence in situ hybridization assay (FISH) were compared in patients who were treated with crizotinib based on their positive ALK rearrangements.

      Results:
      1010 patients were included in this study. Among them, 104 patients were ALK qRT-PCR positive and 53 of them received crizotinib treatment. Among 255 tumors simultaneously analyzed by FISH and RT-PCR, the latter successfully detected all the 25 tumors with arrangements, including two cases which were missed by FISH. The overall response rate (ORR) and median progression free survival (mPFS) of the 53 patients with ALK rearrangements who received crizotinib treatment were 60.4% (95%CI, 47.2-73.6) and 8.4 months (95% CI 6.75-10.05) respectively, which were similar to the 21 patients detected by FISH with ORR of 57.1% (95% CI 33.3-76.2) (p=0.799) and mPFS of 7.4 months (95% CI 4.43-10.38) (p=0.833) after crizotinib treatment. Interestingly, there were 2 patients responded to crizotinib had their ALK rearrangement detected by qRT-PCR but not FISH.

      Conclusion:
      qRT-PCR should be considered as an alternative assay to detect ALK fusion oncogene in NSCLC patients who might be benefit from crizotinib treatment.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P3.04-049 - HER-2 Mutations in Chinese Lung Adenocarcinoma Patients with Negative EGFR Mutations (ID 1345)

      09:30 - 09:30  |  Author(s): C. Zhou

      • Abstract

      Background:
      To determine the prevalence and clinicopathological features of epidermal growth factor receptor 2 (HER-2) mutations in Chinese lung adenocarcinoma patients with negative EGFR mutations.

      Methods:
      Formalin-fixed and paraffin-embedded (FFPE) tissue sections from 398 lung adenocarcinoma patients with wild-type EGFR were screened for HER-2 mutations by amplification refractory mutation system (ARMS) assay and all HER-2 mutations were validated by direct sequencing. The protein expression of HER-2 was evaluated by immunohistochemistry (IHC). Of the 398 samples, 331 were also detected ALK and ROS1 fusions by multiplex RT-PCR, and all fusions positive were verified by direct sequencing. The relationship between HER-2 mutations and clincopathological features and the prognostic effect of its status on disease free survival (DFS) were analyzed.

      Results:
      21 of 398 (5.3%) harbored HER-2 mutations; 7.6% of 278 samples with triple-negative lung adenocarcinoma ( EGFR-, ALK-, ROS1-) were found to have HER-2 mutations. 17 samples (81.0%) were A775_G776insYVMA, two with G776>VC, one with V777_G778insGSP and the last one with 2340_2341ins12 in-frame insertions of exon 20. 59 of 398 (14.8%) were positive of HER-2 expression. No association was found between HER-2 mutations and expression, only two patients coexisted the positive in mutation and expression. There was no statistically significant difference in age, sex, smoking history, and pathological stage between patients with HER-2 mutations and those with negative patients. The DFS of patients with HER-2 mutations have no significant difference compared with those patients with negative mutations.

      Conclusion:
      5.3% of Chinese lung adenocarcinoma with wild-type EGFR harbored HER-2 mutations. The HER-2 mutations had no association with HER-2 expression.