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S. Lu



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    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
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      JCHS.04 - Current Status of Molecular Testing in China: Application and Technology (ID 3454)

      S. Lu

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MINI 08 - Prognostic/Predictive Biomarkers (ID 106)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI08.05 - A Survival Comparison Study of Chinese Patients with Primary Lung Adenocarcinoma Harboring ALK Rearrangements Detected in Different Methods with Crizotinib Treatment (ID 3227)

      S. Lu

      • Abstract
      • Presentation
      • Slides

      Background:
      EML4-ALK is a new driver gene of non-small cell lung cancer (NSCLC) and is associated with response to inhibition with crizotinib. ALK break apart fluorescence in situ hybridization (FISH) assay, Ventana immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR) can all be used as the primary assay for detecting ALK fusion events in tumor samples of lung cancer patients with SFDA approval in China. The objective of this study was to analyze the association of ALK rearrangements with clinical outcomes in different ALK testing methods, including FISH, Ventana IHC, and RT-PCR.

      Methods:
      ALK status was assessed by FISH, IHC and RT-PCR in 75 patients with advanced ALK-positive lung adenocarcinoma who had received crizotinib treatment from 2011, May to 2014, Nov in China. Clinicopathologic data and survival outcomes were analyzed. Kaplan-Meier cumulative probability was used to assess different testing methods for survival.

      Results:
      Of all 75 ALK-positive lung adonocarcinoma, there are 23 FISH-positive ALK patients (23/75, 30.7%), 35 IHC-positive ALK patients (35/75, 46.7%) and 17 RT-PCR-positive ALK patients (17/75, 22.7%). 75 patients received crizotinib treatment with IHC-positive and FISH-positive had better progression-free survival (PFS) (P=0.049, Fig A), compared with those with RT-PCR-positive, but not for overall survival (OS) (P=0.074). The median PFS survival for all these 75 patients was 16m, 14m, 8m, respectively, based on the IHC, FISH, and RT-PCR test (Fig A). 23 patients received first-line crizotinib treatment with IHC-positive and FISH-positive had better PFS (P=0.030), compared with those with RT-PCR-positive, but not for OS (P=0.061), either. The median PFS survival for these 23 patients with first-line crizotinib treatment was 12m, 18m, 4.8m, respectively, based on the IHC, FISH, and RT-PCR test. Of all 17 RT-PCR-positive ALK patients, there are 10 E13:A20 fusion type (10/17, 58.8%), 4 E6:A20 fusion type (4/17, 23.5%), 2 E18:A20 fusion type (2/17, 11.8%), and 1 E2:A20 fusion type (1/17, 5.9%). 4 different fusion-type ALK-positive patients detected by RT-PCR received crizotinib treatment with no crizotinib-related PFS significant difference (P=0.312) and no OS difference (P=0.149).Figure 1



      Conclusion:
      ALK-positive patients confirmed by IHC and FISH assay, compared with RT-PCR, maybe have better crizotinib-related PFS. RT-PCR method needs to be further evaluated in clinical practice to identify its role in guiding targeted therapy using crizotinib. And there is no survival difference for different ALK fusion type detected by RT-PCR in our cohort, which need further validation in a large group.

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    ORAL 04 - Adjuvant Therapy for Early Stage Lung Cancer (ID 99)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      ORAL04.02 - Research of Vascular Targeted Therapy in the Postoperative Adjuvant Chemotherapy for Lung Cancer (ID 1339)

      S. Lu

      • Abstract
      • Presentation
      • Slides

      Background:
      Postoperative adjuvant chemotherapy is extensively received due to its extension of the time to recurrence and enhancement of survival rate in NSCLC. However, it has reached the plateau presently, the beneficial cases are few, and drug-resistance and over-treatment phenomena are in most of patients, hence it is necessary to seek new postoperative adjuvant chemotherapy to improve the survival rate. Angiogenesis is one premise of occurrence, development and metastasize of malignant tumors, but VEGF is one of the most important tumors in the process of neovascularization. Under normal conditions, VEGF is hardly expressed in a lot of normal tissues in vivo, while highly expressed in the tumors. Endostatin can significantly intervene the angiogenesis-promoting effect to block the nutritional supply for tumors and inhibit tumor proliferation or metastasis. We compare the curative effect of endostatin plus adjuvant chemotherapy and adjuvant chemotherapy alone in the treatment of patients with completely resected NSCLC at stage IB-IIIA.

      Methods:
      This is an open, multicenter, randomized (1:1) study, stratified by gender, stage and histology. Completely resected pts (stage IB to IIIA) were randomized to receive adjuvant NP plus Endostatin (Vinorelbine 25mg/m2 on d1 and d8 plus Cisplatin 75 mg/m2 on d1, and iv plus endostatin 7.5mg/m2 per day iv for consecutive 14 days, every 21 days as one cycle, 4 cycles in total) or NP regimen alone. The primary endpoint was disease-free survival (DFS). Secondary endpoints included tumor response rate, overall survival and safety.

      Results:
      250 pts (1:1) were included from 07/2007 to 06/2009. Two arms were well-balanced with regard to age, gender, histology, staging, and resection type. The follow-up time was 60 months. The two groups had no significant difference in the incidence of toxicity reaction. Endostatin plus NP can prolong the DFS of patients with completely resectable NSCLC at stage IIIA with high security, but with no statistical difference (19.33±3.73 m vs 17.10±9.68 m). Cases with high expression of VEGF showed a better DFS than cases with low expression in endostatin plus NP group (48.45±3.52m vs 40.18±4.54m, P < 0.05). The level of peripheral circulating endothelial progenitor cells (EPCs) in NSCLC patients was significantly higher than that in healthy volunteers. EPCs level was associated with NSCLC stage. The EPCs levels after treatment significantly decreased than that before treatment (P=0.014) in beneficiaries of NP or NP plus with endostatin. The time to progression (TTP) was longer in patients with lower levels of EPCs (<0.35%) before chemotherapy or endostatin treatment (P<0.001). However, no statistically significant difference in OS was noticed between the two arms (P = 0.962). The survival rate of endostatin plus NP group was higher for patients in stage IIIA NSCLC, but the differences did not reach statistical significance (MST 41.267 months vs 39.533 months, P = 0.760).

      Conclusion:
      Vascular targeted therapy could prolong the DFS of patients with complete resectable NSCLC in stage IIIA, but did not show benefits in OS for stage IB−IIIA. We shall develop new strategies to identify the patient subgroups that will be benefited or harmed by vascular targeted therapy.

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    ORAL 32 - EGFR WT and MT Targeting (ID 144)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 2
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      ORAL32.01 - Tumor Genomic Analysis from LUX-Lung 8: A Phase III Trial of Afatinib versus Erlotinib in Squamous Cell Carcinoma of the Lung (ID 1401)

      S. Lu

      • Abstract
      • Presentation
      • Slides

      Background:
      Overexpression of EGFR and other ErbB receptors, and/or dysregulation of their downstream pathways are implicated in the pathogenesis of squamous cell carcinoma (SCC) of the lung, generating interest in exploring EGFR/ErbB-targeted agents in this setting. Recent analyses from the global LUX-Lung 8 trial (n=795) in patients with SCC of the lung demonstrated that second-line afatinib (an irreversible ErbB family blocker) conferred overall survival (OS; median 7.9 vs 6.8 months; HR [95% CI] 0.81 [0.69‒0.95]; p=0.008) and progression-free survival (PFS; median 2.6 vs 1.9 months; HR [95% CI] 0.81 [0.69‒0.96]; p=0.010) benefit over erlotinib (a reversible EGFR inhibitor). To assess biomarkers for efficacy for these agents in SCC we conducted an exploratory analysis using archival tumor tissue collected at time of study entry.

      Methods:
      Among all randomized patients, samples were retrospectively enriched for those from patients with PFS >2 months and appropriate controls (PFS ≤2 months; Figure 1) and were selected for analysis using the Foundation Medicine (FM) FoundationOne™ next-generation sequencing (NGS) platform (n=433); 300 cancer-related genes were analyzed for copy number alterations (CNAs), rearrangements and single nucleotide variants (SVs). Preliminary results from the 238 samples analyzable so far (~30% of the randomized patients), focusing on genomic alterations of EGFR and their potential association to survival endpoints PFS and OS, are presented.

      Results:
      Fourteen EGFR SVs (5.8%) were detected of which 10 were novel with unknown clinical significance (Figure 1). Figure 1 Four had been previously reported; 2 (E114K [afatinib arm], Q1021* [erlotinib arm]) occurred in the non-kinase domains and 2 (L861Q [afatinib arm], L858R [erlotinib arm]) in the kinase domain. The frequency of EGFR CNAs (n=15 [6.3%]; afatinib: 9; erlotinib: 6) was also low. At the time of these ongoing analyses, these low frequencies of EGFR mutations/amplifications were deemed not to be associated with the observed improvements in PFS and OS. Genomic alterations aggregated across two key gene groups (ErbB and FGF families) and their association with survival outcomes will be presented.



      Conclusion:
      The frequency of EGFR genomic aberrations in the samples tested was low. Based on this analysis of a subgroup of patients, PFS and OS improvements conferred by afatinib in LUX-Lung 8 were not driven by the presence of activating EGFR mutations or amplifications and may be related to afatinib’s ability to inactivate multiple aberrant signaling cascades associated with, and downstream of, ErbB receptors.

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      ORAL32.06 - Intercalating and Maintenance Use of Gefitinib plus Chemotherapy versus Chemotherapy Alone in Selected Advanced NSCLC: A Phase III Study (ID 2108)

      S. Lu

      • Abstract
      • Presentation
      • Slides

      Background:
      This study investigated whether intercalating and maintenance use of gefitinib with chemotherapy improves clinical outcomes versus chemotherapy alone in selected, chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) after receiving two cycles of gemcitabine plus carboplatin with stable disease.

      Methods:
      We undertook an open-label, randomized, phase III trial at 14 centres in China. Non-smoking patients with previously untreated stage IIIB/IV lung adenocarcinoma with EGFR mutation status unknown (tissue not available) firstly received two cycles of gemcitabine (1,250 mg/m2 days 1 and 8) plus carboplatin (AUC=5, day 1). The patients with stable disease and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive either gefitinib (250mg/d) on days 15 to 25 with a 4-week cycle of gemcitabine and carboplatin or a 4-week cycle of gemcitabine and carboplatin alone. A maximum of four cycles of chemotherapy was allowed in both arms after which time patients continued to receive gefitinib or observation until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. The trial is registered at ClinicalTrials.gov, number NCT01404260, and has completed enrolment; patients are still in follow-up.

      Results:
      From June 2011 to August 2014, 219 patients with stable disease were randomized to intercalating and maintenance use of gefitinib with chemotherapy (n=109) or chemotherapy alone (n=110). The number of PFS events is 84 cases for the gefitinib plus chemotherapy group and 93 cases for the chemotherapy alone group. PFS was significantly longer in the patients receiving gefitinib and chemotherapy than in those receiving chemotherapy alone (median 10.0 vs 4.4 months, respectively; hazard ratio 0.475, 95% CI 0.349-0.646; p<0.0001). The median follow-up duration for OS is 24.5 months; OS of maturity 34.7% was not statistically different between these two arms (32.2 vs 32.5 months, respectively; hazard ratio 1.01, 95% CI 0.64-1.58; p=0.97). The addition of gefitinib to chemotherapy was well tolerated, with no increase in haematologic toxicity and no treatment-related interstitial lung disease.

      Conclusion:
      Intercalating and maintenance use of gefitinib with gemcitabine/carboplatin led to a significant improvement in PFS versus gemcitabine/carboplatin alone for Chinese nonsmoking patients with advanced pulmonary adenocarcinoma (EGFR mutation status unknown) who had previously achieved stable disease after receiving two cycles of gemcitabine/carboplatin; immature OS was not statistically different.

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

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-023 - Discrepancy of ALK Status in Lung Adenocarcinoma Subtypes According to the IALSC/ATS/ERS Classification in Chinese Patients (ID 2213)

      S. Lu

      • Abstract
      • Slides

      Background:
      This study aimed to determine the relationship between ALK status and predominant subtype, according to the IALSC/ATS/ERS classification.

      Methods:
      A reclassification of 638 surgically resected adenocarcinomas was performed in Shanghai Chest Hospital. ALK Status was detected by immunohistochemistry (Ventana Medical Systems) in these patients.All of the cases were confirmed by two independent pathologists.

      Results:
      The most prevalent subtype was acinar predominant (46.0%), followed by papillary predominant (25.2%), solid predominant (9.2%), micropapillary predominant (8.7%), variants of invasive adenocarcinoma (5.5%), lepidic predominant(5.3%), minimally invasive adenocarcinoma(2.0%), and adenocarcinoma in situ(1.0%). ALK positive was identified in 29 of 638 tumors (4.5%). The ALK positive frequencies were: 3.0%(8/284) for acinar predominant, 1.9%(3/156) for papillary predominant, 12.3%(7/57) for solid predominant, 5.3%(3/54) for micropapillary predominant, 17.6%(6/34) for variants of invasive adenocarcinoma, 3.0%(1/33) for lepidic predominant, 7.7%(1/13) for minimally invasive adenocarcinoma, and 0%(0/7) for adenocarcinoma in situ, respectively. ALK positive was significantly associated with the solid predominant subtype(p=0.003) and variants of invasive adenocarcinoma(p=0.0002).

      Conclusion:
      The ALK positive frequencies of solid predominant subtype and variants of invasive adenocarcinoma were higher than other subtypes.

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

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

      S. Lu

      • 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.

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      P2.01-066 - A Prospective, Randomized, Multicenter, Phase III Study, Comparing rhTPO with rhIL-11 Treating CIT - An Interim Analysis (NCT02344979) (ID 1178)

      S. Lu

      • Abstract
      • Slides

      Background:
      Chemotherapy-induced thrombocytopenia (CIT) has seriously hindered the application of anti-cancer drugs. Thrombopoietic factors such as recombinant human interleukin-11(rhIL-11), thrombopoietin and its derivative(recombinant human thrombopoietin, rhTPO) are routinely administrated for CIT. But there is no randomized study to compare rhTPO with rhIL-11 on efficacy and safety of thrombocytopenia prophylactic treatment before. This is the first randomized, open-label, multicenter, phase Ⅲ study to compare them in China. We tried to investigate the efficacy and safety of prophylactic administration with rhTPO or rhIL-11 to prevent CIT in advanced non-small-cell lung cancer(NSCLC) patients.

      Methods:
      From June 2009 to February 2015, 71 patients with advanced NSCLC who were receiving the first-line platinum-based chemotherapy suffered severe thrombocytopenia(the nadir of platelet counts<50×10[9]/L, confirmed by two times of blood routine in different days) during prior chemotherapy cycle. They were randomized to rhTPO arm or rhIL-11 arm in the following chemotherapy cycle, and the chemotherapy regimens and drug doses were consistent in the prior and following cycle (GC Gemcitabine 1000-1250 mg/m[2], D1 and D8; Carboplatin dosing by AUC value=5, D1; Q3W) or GP (Gemcitabine 1000-1250 mg/m[2], D1 and D8; Cisplatin 75 mg/m[2], D1; Q3W). 49 patients (34 males, 15 females) were enrolled rhTPO arm and 22 patients (14 males, 8 females) were enrolled rhIL-11 arm. There were no statistical difference between two arms in terms of gender[34 males(69.4%) vs.14 males(63.6%),P>0.05], age(58.5±9.3 yrs vs. 60.3±7.5 yrs, P>0.05), and the nadir of platelet counts during prior chemotherapy cycle(31.4±13.1×10[9]/L vs. 28.6±12.8×10[9]/L, P>0.05). rhTPO (15000U/d) was injected subcutaneously on the 2[nd], 4[th], 6[th], 9[th ]Day after the initiation of chemotherapy, and IL-11(3mg/d) was injected subcutaneously per day from Day 9 to Day15 after the initiation of chemotherapy. Blood routines were conducted to test before chemotherapy initiation and the 3[th], 5[th], 7[th], 9[th], 11[th], 13[th], 15[th], 17[th], and 21[th] day after chemotherapy. Toxicity and efficacy were monitored.

      Results:
      In the following chemotherapy cycle there were no statistical difference between rhTPO arm and rhIL-11 arm on the following indexes: the nadir of platelet counts(66.6±43.1×10[9]/L vs. 53.8±40.6×10[9]/L, P>0.05) , the maximum platelet counts (219±132×10[9]/L vs. 240±151×10[9]/L, P>0.05) , duration of platelet counts less than 50×10[9]/L[Median (95%CI): 4.0(3.0-5.0) days vs. 4.5(3.0-6.0) days, P>0.05], time of platelet count recovered to 75×10[9]/L [Median(95%CI): 2(2-3) days vs. 3(0-4) days, P>0.05] and to 100×10[9]/L[median(95%CI): 4(3-6) days vs. 4.5(3-8) days, P>0.05]. Drug-related adverse events in rhTPO arm were less than that of rhIL-11 arm (5 cases(10.2%) in rhTPO arm, 7 cases(31.8%) in rhIL-11 arm, P<0.05).

      Conclusion:
      Although there is no statistical difference on efficacies, prophylactic administration of rhTPO is safer and more convenient than that of rhIL-11 in advanced NSCLC patients. This is an interim analysis. More data is still waiting.

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    P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P2.03-031 - Subgroup Analysis of East Asian Patients in the Phase III PROCLAIM Trial (ID 1293)

      S. Lu

      • Abstract

      Background:
      PROCLAIM is a phase III trial comparing overall survival (OS) in patients with stage III, unresectable, nonsquamous non-small cell lung cancer (NSCLC) receiving pemetrexed (Pem) plus cisplatin (Cis) and concurrent thoracic radiation therapy (TRT) for 3 cycles followed by 4 cycles of Pem consolidation (Pem+Cis arm) versus etoposide (Etop) plus Cis and concurrent TRT for 2 cycles followed by up to 2 cycles of consolidation with a platinum-based doublet of choice (Etop+Cis arm). Overall efficacy and safety results for the intent-to-treat (ITT) population (N=598) will be presented in a separate disclosure. Efficacy and safety results from an East Asia (EA) subgroup analysis are presented here.

      Methods:
      A subgroup analysis was performed using the EA randomized population (N=97), which consisted of all patients who were randomized to the study from China (n=61), Taiwan (n=25), and The Republic of Korea (n=11). OS and progression-free survival (PFS) were evaluated by the Kaplan-Meier method and hazard ratios (HRs) were calculated using a Cox regression model. The log-rank test was used to compare treatment arms. Objective response rates (ORRs) were compared using an unadjusted, normal distribution approximation for the difference in rates. ClinicalTrials.gov number NCT00686959.

      Results:
      Baseline characteristics were balanced between treatment arms for EA patients. In the 97 randomized EA patients (n=44 in the Pem+Cis arm; n=53 in the Etop+Cis arm), median PFS was 10.0 months for the Pem+Cis arm and 7.6 months for the Etop+Cis arm (HR: 0.97, 95% confidence interval [CI]: 0.61–1.54, p=0.890). The censoring rate was high for OS (Pem+Cis arm: 43.2%; Etop+Cis arm: 52.8%), and there was no significant difference in OS between the Pem+Cis arm and the Etop+Cis arm (HR: 1.23, 95% CI: 0.70–2.14, p=0.469). The interaction test for region and treatment effect for OS was not significant (p=0.374). The ORRs were 47.7% (95% CI: 32.46–63.31) in the Pem+Cis arm and 34.0% (95% CI: 21.52–48.27) in the Etop+Cis arm. In the 90 treated EA patients (n=44 in the Pem+Cis arm; n=46 in the Etop+Cis arm), the overall incidence of drug-related grade 3/4 treatment-emergent adverse events (TEAEs) was significantly lower in the Pem+Cis arm versus the Etop+Cis arm (61.4% vs. 91.3%; p=0.001). All drug-related grade 3/4 TEAEs occurring in ≥5% of patients had a numerically lower incidence in the Pem+Cis arm than in the Etop+Cis arm except lymphopenia (17 [38.6%] vs. 17 [37.0%]).

      Conclusion:
      For EA patients with nonsquamous NSCLC, Pem+Cis did not improve OS, but did have a good safety profile and numerically improved PFS and ORR compared to Etop+Cis.

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

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 3
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      P3.01-006 - Propensity Score Matched Comparison of EGFR TKI for EGFR Mutation 19del vs 21L858R  (ID 2319)

      S. Lu

      • Abstract
      • Slides

      Background:
      Previously, data of Lux-lung 3 and Lux-lung 6 showed overall survival was improved with the afatinib for patients with 19del EGFR mutations and the absence of an effect in patients with L858R EGFR mutations suggests that EGFR 19del-positive disease might be distinct from L858R-positive disease. We aimed to assess the effect of first-generation reverse EGFR TKI (Gefitinib and Elotinib) on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from real world practice.

      Methods:
      This is a retrospective study, 134 patients with EGFRm 19del or 21L858R with reverse EGFR TKI gefitinib or elotinib in clinical practice from Jun.2012 to April.2014 in Shanghai Chest Hospital , follow-up to April.1,2015. To control for selection bias, matched groups of patients were selected using a propensity score matching method. Overall survival and PFS were estimated using the Kaplan-Meier method with log-rank test. The Wilcoxon rank sum test was used for variables not normally distributed. Categorical data are displayed as frequencies and comparisons were made with Chi-square tests (Fisher exact tests if appropriate).

      Results:
      After1:1 the propensity score matching, matching was based on a one-to-two nearest neighbor matching method with a tolerance level on the maximum propensity score distance (calipers of width 0.2 standard deviation of the logit of the PS). 70 patients were enrolled, the baseline variables (eg, age, sex, smoking , PS, line of EGFR TKI treatment ) were comparable between the matched cohorts (P > 0.05 for all). Follow-up time: 19del (median 16.2 months, range 1.0-49.2) , 21L858R (median 16.4 months, range 0.4-41.1). m PFS in 19 del and 21L858R was 16.3months, 16.8months, respectively, m OS in 19 del and 21L858R was28.4 months, 32.2 months, respectively, There are no significant difference between EGFR mutation 19del and 21L858R patients with the reversible first-generation inhibitors.

      Conclusion:
      CONCLUSION: There are no significant difference between EGFR mutation 19del and 21L858R patients with the reversible first-generation inhibitors either PFS or OS. The results maybe related to the sample size, waiting for the results of meta-analysis.

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      P3.01-010 - Multivariate Survival Analysis of China IRESSA Charitable Aid Project in Shanghai (ID 2671)

      S. Lu

      • Abstract
      • Slides

      Background:
      Since Jan 2007, China Charity Federation launched IRESSA Charitable Aid Project for advanced non small cell lung cancer which oral IRESSA was effective for 6 months and have failed previous chemotherapy or received first line IRESSA for EGFR mutation positive. This study investigated the survival and correlation influencing factor of China Charitable Aid Project in shanghai by COX multivariate analysis .

      Methods:
      A retrospective investigation enrolled advanced non small cell lung cancer patient of IRESSA Charitable Aid Project from Jan 2007 to 30 Jun 2013 at 7 centre in Shanghai . The patients oral IRESSA was effective for 6 months who have failed previous chemotherapy or received first line IRESSA for EGFR mutation positive. IRESSA 250mg QD was taken and prescribed monthly. Tumor assessment was performed every 8 weeks, patients continued to receive IRESSA until disease progression (timely withdraw) or unacceptable toxicity or no benefit from this project which was considered as slower progression(late withdraw). The patient were Followed up until 30 Aug 2014. The primary end point was OS and correlation influencing factor. Using the Kaplan-Meier and COX proportional hazards model analyze the correlation between survival and age, gender, smoking status, pathology, indications and timely withdraw of IRESSA.

      Results:
      A total of 1066 patients were enrolled, the median age was 64, including 339 cases of greater than or equal to 70. Most patients were female (845,79.3%) and no-smokers (992,93.1%), and 94.1% was adenocarcinoma. Indication for second and multiple line patients were 96.1%(1024). The midian PFS was 33 months (95%CI:29.8-36.2),and the MST was 37 months (95%CI:32.5-41.5). COX multivariate analysis revealed timely withdraw group was significantly longer OS ( hazard ration 1.627; 95%CI:1.378-1.922, p=0.000) , more than 70 years old, smoking and indication for second line patient was significantly worse OS (hazard ration 0.692; 95%CI:0.587-0.816, p=0.000; 0.714; 95%CI: 0.531-0.960, p=0.026; 0.498 ;95%CI: 0.265-0.935,p=0.03 respectively.

      Conclusion:
      96.1% of the patient in Iressa charitable aid projects were second or multiple line treatment due to chemotherapy failure, PFS and OS still reached 33 and 37 months, significantly better than the historical reports. The possible reason was enrolled patients with IRESSA effective for 6 months , It could be EGFR mutation positive, of which no-smoking patients ratio were as high as 93.1%, they maybe have a better prognosis. Multivariate analysis showed OS was significantly prolonged in timely withdraw group after disease deteriorate.

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      P3.01-050 - A Interim Analysis of Randomized Phase III Trial of Nedaplatin or Cisplatin Combined with Docetaxel as First-Line Treatment for Advanced ASQC (ID 1225)

      S. Lu

      • Abstract
      • Slides

      Background:
      Cisplatin combined with docetaxel is one of the stand treatment in advanced squamous cell carcinoma(ASQC) of the lung. Nedaplatin combined with docetaxel has demonstrated potent activity in ASQC in phase II study. But until now there is no randomized phase III study comparing these 2 chemotherapy regimens. The aim of this study was to evaluate and compare the efficacy and safety between the combination chemotherapy of nedaplatin or cisplatin plus docetaxel in patients with ASQC.

      Methods:
      This is a multicentre, open-label, randomized, phase III study in China (NCT02088515). Chemo-naive stage IIIB/IV squamous NSCLC with Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of nedaplatin (80 mg/m[2]) plus docetaxel(75 mg/m[2]) or cisplatin(75 mg/m[2]) plus docetaxel (75 mg/m[2]) . The primary endpoint was progression-free survival (PFS). Secondary end points were overall survival (OS), overall response rate (ORR), disease control rate (DCR) and quality of life.

      Results:
      From December 2013 to January 2015, 117 patients were accrued: nedaplatin plus docetaxel (n = 57) and cisplatin plus docetaxel (n = 60). The objective response rates were 27% and 31% and the disease control rate were 78.92 % and 82.67% in nedaplatin and cisplatin groups, respectively. There is no significance difference in nausea / vomiting(21% vs 30%) , diarrhea(3% vs 5%), liver dysfunction(12% vs 15%), neutropenia(60% vs 65%), thrombocytopenia(10% vs 12%), anemia(8% vs 7%) between the 2 arms. The renal dysfunction incidence is higher in the cisplatin group(3% vs 0%). Although there is no 3/4 grade toxicities difference between 2 arms including nausea / vomiting(0% vs 0%) , diarrhea(0% vs 1%), liver dysfunction(0% vs 0%), renal dysfunction(0% vs 0%) , neutropenia(4% vs 3%), thrombocytopenia(0% vs 0%), anemia(0% vs 0%) . This is an interim analysis and we haven't got the data of survival and quality of life.

      Conclusion:
      There is no ORR difference between the group of nedaplatin plus docetaxel and cisplatin plus docetaxel. But the toxicity of nedaplatin regiment is less toxicities, especially in renal toxicity,as first-line treatment for patients with advanced squamous NSCLC

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    P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P3.03-017 - Interim Overall Survival of Neoadjuvant Erlotinib Intercalated with Gemcitabine/Cisplatin for IIIA N2 NSCLC Patients: A Phase II Study (ID 1743)

      S. Lu

      • Abstract

      Background:
      The optimal treatment for locally advanced stage IIIA non-small cell lung cancer (NSCLC) disease is not well established although neoadjuvant chemotherapy showed active results in stage IIIA N2 pts. A few case reports also indicate the advantages of neoadjuvant erlotinib. FASTACT II study showed that the regimen of erlotinib intercalated with chemotherapy improved PFS and OS in an unselected advanced NSCLC population of east Asian patients. Here we report the interim overall survival (OS) results of a phase II study which was to assess the efficacy and safety profile of erlotinib intercalated with gemcitabine/cisplatin as neoadjuvant treatment in stage IIIA N2 NSCLC pts.

      Methods:
      Patients with untreated stage IIIA bulky N2 NSCLC and ECOG PS 0/1 were enrolled to received up to 2 cycles of gemcitabine 1,000 mg/m[2] on days 1 and 8 and cisplatin 75 mg/m[2] on day 1 or carboplatin AUC=5 d1, followed by oral erlotinib (150 mg, once a day) on days 15 to 28 as neoadjuvant therapy. A repeat computed tomography (CT) scan evaluated the response after induction therapy and eligible patients would undergo surgical resection. The primary endpoint was ORR which was reported in 2013 WCLC. The secondary endpoints included pCR, resection rate, DFS (disease free survival) and OS (overall survival), safety, QoL and biomarker analyses.

      Results:
      Between March 2011 and December 2012, a total of 39 patients (29 male, median age 59.0 years; range 34.0 to 74.0 years) were enrolled in the study, in which 36 patients ( 92.3%) had completed 2-cycle erlotinib neoadjuvant treatment. For pathologic type, 13 pts were adenocarcinoma, 18 pts were squamous carcinoma, and 8 pts were other types. One patient withdrew from the study and one patient was lost in the follow-up. Twenty-two (56.4%, 22/39) patients underwent surgical resection after erlotinib neoadjuvant treatment. Till Jan 15, 2015, the median follow up duration was 24.4 mo (range 5.5 to 43.7 mo). To the cut-off date, 22 patients (56.4%) died. The median OS for total 39 patients was 29.0 mo (Figure 1A, range 3.4 to 43.7 mo). The median OS for those no surgery pts was 17.0 mo (range 6.1 to 39.8 mo) while the median OS is not matured ye for those pts who received surgery (Figure 1B).Figure 1



      Conclusion:
      Neoadjuvant erlotinib intercalated with gemcitabine/cisplatin brought clinical benefits by extending overall survival for stage IIIA N2 NSCLC pts.