Virtual Library

Start Your Search

L. Zhang



Author of

  • +

    MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      MA08.07 - Prospective Sequential Counts of Total CTC or cKIT+CTC in Advanced NSCLC with 1st Line Chemotherapy (POLICE) (ID 5857)

      11:00 - 12:30  |  Author(s): L. Zhang

      • Abstract
      • Presentation
      • Slides

      Background:
      Circulating tumor cells (CTCs) have been reported prognostic and predictive in non-small cell lung cancer (NSCLC) and a few of other cancer types. In 1[st] line setting, whether EPCAM[+]CK[+]CD45[-] CTC and/or stem cell-like cKIT[+]EPCAM[+ ]CK[+]CD45[-] CTC enumeration and dynamic changes can be prognostic and/or predictive to standard chemotherapy need further investigation in Chinese patients with NSCLC.

      Methods:
      A prospective study on the CTC enumeration in advanced NSCLC with 1st line chemotherapy (POLICE) was started by China Thoracic Oncology Group (CTONG). Patients with NSCLC naïve for systemic regimens were enrolled since August 2013. CTCs were detected by Cell Search Platform and identified as positive for EPCAM[+]CK[+]CD45[-] phenotype. CD117 (cKIT) marker was added to test the frequency of stem cell-like cKIT[+]EPCAM[+]CK[+]CD45[- ]CTCs. Primary endpoints were CTC counts and its correlation with first line therapy.

      Results:
      Totally 180 patients were enrolled. In 174 case total CTC and cKIT[+]CTC positive (cutoff >=1) rates were 38.5% (67/172) vs 14.3% (24/168), 21.8% (31/142) vs 6.3% (9/142), 13.7% (13/95) vs 6.4% (6/94) and 40.4% (38/94) vs 15.0% (13/93) at time-points of baseline, after first-cycle-chemo, after four-cycles-chemo and disease progression. At time immediately after first-cycle-chemo, patients in CTC=0 group got statistically higher ORR (29.0% VS 7.1%, P=0.017) and DCR (74.2% VS 42.9%, P=0.002) than in CTC>=1 group. At time after four-cycles-chemo, patients in CTC=0 group got statistically higher DCR (88.3% VS 58.3%, P=0.026) than in CTC>=1 group. At time either after first-cycle-chemo or after four-cycles-chemo, patients in CTC>=1 group got worse PFS (5.7m VS 4.0m, P=0.025; 6.3m VS 4.0m, P=0.001 ) than in CTC=0 group. At time after first-cycle-chemo, patients in groups cKIT[+]CTC>=1 and cKIT[-]CTC>=1 got worse PFSs (3.1m vs 4.0m vs 5.7m, P=0.001) and worse DCRs (44.4% vs 42.1% vs 73.9%, P=0.009) than in CTC=0 group. For 142 patients categorized into three groups of dynamic CTC decrease (17), CTC unchanged (82), and CTC increase (43), there were significant differences in terms of DCR (71.8% vs 71.6% vs 33.3%, P=0.018) and PFS (5.2m vs 5.6m vs 3.1m, P=0.037).

      Conclusion:
      In first line setting of advanced NSCLC, at time-points after first-cycle-chemo other than baseline, total CTC or cKIT[+]CTC counts could be predictive for worse DCR or PFS. CTC increase from baseline to after-first-cycle-chemo might be a strong signal for the inefficacy of first line chemotherapy in the NSCLC patients.

      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.

  • +

    OA23 - EGFR Targeted Therapies in Advanced NSCLC (ID 410)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • +

      OA23.05 - First-Line Afatinib versus Gefitinib in EGFRm+ Advanced NSCLC: Updated Overall Survival Analysis of LUX-Lung 7 (ID 5347)

      14:20 - 15:50  |  Author(s): L. Zhang

      • Abstract
      • Presentation
      • Slides

      Background:
      The irreversible ErbB family blocker afatinib and the reversible EGFR TKI gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. This Phase IIb trial prospectively compared afatinib versus gefitinib in this setting.

      Methods:
      LUX-Lung 7 assessed afatinib (40 mg/day) versus gefitinib (250 mg/day) in treatment-naïve patients with stage IIIb/IV NSCLC harbouring a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS (independent review), time to treatment failure (TTF) and OS. Other endpoints included ORR and AEs. In case of grade ≥3/selected grade 2 drug-related AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum). The primary analysis of PFS/TTF was undertaken after ~250 PFS events. The primary OS analysis was planned after ~213 OS events and a follow-up period of ≥32 months.

      Results:
      319 patients were randomised (afatinib: 160; gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57‒0.95], p=0.017), TTF (0.73 [0.58‒0.92], p=0.007) and ORR (70 vs 56%, p=0.008) were significantly improved with afatinib versus gefitinib. The most common grade ≥3 AEs were diarrhoea (13%) and rash/acne (9%) with afatinib and elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib had ≥1 dose reduction due to AEs; dose reductions were more common in females than males (77%/23%) and non-Asians than Asians (64%/36%). Dose reduction of afatinib did not negatively impact PFS (<40mg vs ≥40mg; HR [95% CI]: 1.34 [0.90‒2.00]) but reduced incidence and severity of drug-related grade ≥3 AEs. Treatment discontinuation due to drug-related AEs was the same in each arm (6%). The data cut-off for primary OS analysis occurred on 8 April 2016. At this time, median treatment duration (range) was 13.7 (0‒46.4) versus 11.5 (0.5‒48.7) months with afatinib and gefitinib. 25% (afatinib) and 13% (gefitinib) of patients received treatment for >24 months. 73% and 77% of patients in the afatinib and gefitinib arms had ≥1 subsequent systemic anti-cancer treatment, with 46% and 56% receiving a subsequent EGFR-TKI including osimertinib (14%)/olmutinib (14%). OS data, including subgroup analysis with respect to subsequent therapy will be presented at the meeting.

      Conclusion:
      Afatinib significantly improved PFS, TTF and ORR versus gefitinib in EGFRm+ NSCLC patients, with a manageable AE profile and few drug-related discontinuations. Dose adjustment of afatinib reduced drug-related AEs without compromising efficacy. Primary OS analysis will be reported.

      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.

  • +

    P2.06 - Poster Session with Presenters Present (ID 467)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
    • +

      P2.06-033 - Long-Term Safety and Efficacy of Darbepoetin Alfa in Subjects with Advanced Stage NSCLC Receiving Multi-Cycle Chemotherapy (ID 3765)

      14:30 - 15:45  |  Author(s): L. Zhang

      • Abstract

      Background:
      Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) that has been shown to increase hemoglobin levels and reduce the rate of transfusions in patients with chemotherapy-induced anemia (CIA). Most studies have not shown an association between ESA use and poor outcomes, but some clinical trials have reported increased mortality and/or tumor progression. This trial was therefore designed to address the safety of DA for CIA in patients with non-small cell lung cancer (NSCLC).

      Methods:
      Study 20070782 is a randomized, double-blind, noninferiority trial to compare DA with placebo, and is enrolling patients with NSCLC with CIA. Eligible patients are ≥ 18 years old with Eastern Cooperative Oncology Group (ECOG) status ≤ 1, stage IV NSCLC, no prior adjuvant/neoadjuvant NSCLC therapy, ≥ 2 cycles first-line chemotherapy planned (≥ 6 weeks total), and screening hemoglobin ≤ 11 g/dL. Approximately 3,000 patients from up to 500 global sites will be randomized 2:1 to DA (500 mcg) or placebo every 3 weeks (Q3W) until disease progression or end of chemotherapy. At hemoglobin > 12 g/dL, study drug is withheld until hemoglobin ≤ 12 g/dL. Transfusions are allowed when necessary. Endpoints include overall survival (OS; primary) and progression-free survival (PFS; secondary), and will be analyzed when ~2,700 deaths have occurred. Additional safety endpoints include tumor response and rate of thromboembolic events. Superiority of DA to placebo in transfusion rates will be tested if noninferiority is achieved for OS and PFS.

      Results:
      As of April 15, 2016, a total of 2,215 patients have enrolled. The independent data monitoring committee has conducted 9 reviews of unblinded data (which included a planned formal interim analysis at 40% of planned total number of 2,700 deaths to test for harm), and has recommended continuation of the trial without changes.

      Conclusion:
      Study 20070782 is the largest clinical trial in NSCLC to date, and will provide comprehensive data on the safety and efficacy of DA in patients with CIA.

  • +

    P3.02b - Poster Session with Presenters Present (ID 494)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 2
    • +

      P3.02b-044 - Afatinib versus Gefitinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients Aged ≥75 Years: Subgroup Analysis of LUX-Lung 7 (ID 5327)

      14:30 - 15:45  |  Author(s): L. Zhang

      • Abstract
      • Slides

      Background:
      The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. In the Phase IIb LUX-Lung 7 trial, afatinib significantly improved median progression-free survival (PFS; HR=0.73 [95% CI, 0.57–0.95], p=0.017), objective response rate (70% vs 56%, p=0.008) and time to treatment failure (TTF; HR=0.73 [95% CI, 0.58–0.92], p=0.007) versus gefitinib in this setting (Park et al. Lancet Oncol 2016). Here we evaluated the efficacy and safety of afatinib versus gefitinib in patients aged ≥75 years in a subgroup analysis of LUX-Lung 7 (NCT01466660).

      Methods:
      Treatment-naïve patients with stage IIIB/IV EGFRm+ NSCLC were randomized (1:1) to oral afatinib (40 mg/day) or gefitinib (250 mg/day), stratified by EGFR mutation type (Del19/L858R) and presence of brain metastases (Yes/No). Co-primary endpoints were PFS, TTF, and overall survival. Subgroup analyses of PFS and adverse events (AEs) by age (≥75/<75 years) were exploratory.

      Results:
      Of 319 patients randomised in LL7, 40 (13%) were aged ≥75 years (afatinib n=19, gefitinib n=21). Median PFS for both age groups was in line with the overall population and favoured afatinib versus gefitinib (patients ≥75 years: 14.7 vs 10.8 months, HR=0.69 [95% CI, 0.33–1.44]; patients <75 years: 11.0 vs 10.9 months, HR=0.76 [95% CI, 0.58–1.00]). The incidence of treatment-related AEs (grade 3/4) was slightly higher in the older subgroup (afatinib: 42%/0%; gefitinib: 24%/5%) than in the younger subgroup (afatinib: 28%/2%; gefitinib: 15%/<1%). There were no unexpected safety findings. The most common treatment-related AEs (all grade [grade 3]) with afatinib in the older patient subgroup were diarrhoea (89% [21%]), rash (63% [5%]), dry skin (37% [0%]), and decreased appetite (32% [0%]). Dose reduction/discontinuation of afatinib due to treatment-related AEs was required in 53%/16% and 40%/5% of the older and younger subgroup, respectively.

      Conclusion:
      A small subgroup of patients in the LUX-Lung 7 trial were ≥75 years old (13%). In exploratory subgroup analyses of patients aged ≥75 and <75 years old, advancing age did not adversely affect the PFS benefit and tolerability observed with afatinib versus gefitinib in treatment-naïve EGFRm+ NSCLC patients. These findings suggest that afatinib can provide an effective and tolerable treatment for older patients with EGFRm+ 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.

    • +

      P3.02b-099 - Pharmacokinetics of Osimertinib (AZD9291) in Chinese Patients with Advanced NSCLC: A Phase I Study (ID 4440)

      14:30 - 15:45  |  Author(s): L. Zhang

      • Abstract

      Background:
      Osimertinib is a potent, irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), selective for EGFR-sensitising (EGFRm) and T790M resistance mutations. The Phase I AURA18 study (NCT02529995) assessed osimertinib pharmacokinetics (PK) in Chinese patients with advanced non-small cell lung cancer (aNSCLC) who progressed following prior EGFR-TKI therapy.

      Methods:
      Osimertinib is a potent, irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), selective for EGFR-sensitising (EGFRm) and T790M resistance mutations. The Phase I AURA18 study (NCT02529995) assessed osimertinib pharmacokinetics (PK) in Chinese patients with advanced non-small cell lung cancer (aNSCLC) who progressed following prior EGFR-TKI therapy.

      Results:
      31 patients were treated (Cohort 1, n=15; Cohort 2, n=16): median age, 57.0 years; female, 58%; never smokers, 74%. 26 harboured tumors with the EGFR T790M mutation (local test). The PK analysis set included 25 patients: 6 were excluded due to prior treatment with an osimertinib-like substance or a T790M-directed EGFR-TKI. Osimertinib exposure increased approximately dose-proportionally after single and multiple dosing, similar to previous global studies. 29 (94%) patients experienced at least one adverse event (AE), 3 patients experienced an AE of Grade ≥3; no patients discontinued treatment due to AEs. The most common AEs were: diarrhoea (32%), white blood cell decreased (23%), neutrophil count decreased (19%), dry mouth and erythema (19%). ORR (all partial responses) in T790M mutation-positive subgroup was 36% for Cohort 1 (4/11; 95% CI 11, 69) and 67% for Cohort 2 (10/15; 95% CI 38, 88).

      Conclusion:
      Osimertinib PK in the AURA18 Chinese patient population is consistent with the global population and supports 80 mg once-daily dosing. Clinical benefit and a tolerable safety profile were demonstrated. Figure 1



  • +

    PL03 - Presidential Symposium (ID 428)

    • Event: WCLC 2016
    • Type: Plenary
    • Track:
    • Presentations: 1
    • +

      PL03.05 - BRAIN: A Phase Ⅲ Trial Comparing WBI and Chemotherapy with Icotinib in NSCLC with Brain Metastases Harboring EGFR Mutations (CTONG 1201) (Abstract under Embargo until December 6, 7:00 CET) (ID 4570)

      08:35 - 10:25  |  Author(s): L. Zhang

      • Abstract
      • Presentation
      • Slides

      Background:
      Non-small cell lung cancer (NSCLC) with brain metastases (M) had a poor prognosis. Whole brain irradiation (WBI) is a standard of care for this critical medical condition. The median survival is only 4-6 months. Small molecule inhibitors of epidermal growth factor receptor (EGFR) including icotinib achieved very successful results in advanced NSCLC with EGFR mutations. There were no prospective randomized clinical trials to explore the efficacy of EGFR tyrosine kinase inhibitors (TKIs) on brain M.

      Methods:
      Advanced NSCLC with EGFR sensitive mutations and brain M were randomized to WBI plus chemotherapy (chemo) or icotinib. Patients in WBI arm received radiotherapy with 30Gy/3Gy/10 fractions plus concurrent or sequential doublet chemo of 4-6 cycles. Patients in EGFR TKI arm received icotinib 125mg orally tid until disease progression. Icotinib could be continued beyond progression if clinical benefit was observed by the investigator. Crossover to icotinib from WBI could be permitted. Key inclusion criteria were EGFR mutations and radiologically confirmed brain M with at least 3 lesions. The primary endpoint was intracranial progression-free survival (iPFS) by investigator assessments according to RECIST v1.1. The secondary endpoints included objective response rate (ORR), PFS and overall survival (OS). Safety and tolerability were assessed by measuring adverse events (AEs) (CTCAE v4).

      Results:
      From Dec. 2012 to June 2015, 176 patients from 17 sites were randomized to WBI+Chemo arm (N=91) or icotinib arm (N=85). The baseline clinicopathologic factors were balanced between the two groups. Median age was 58, PS 1 was 87.2%, non-smoker 70.9%, adenocarcinoma 96.8%, symptomatic brain M were 16.5%. Icotinib significantly improved median iPFS compared with WBI+chemo: hazard ratio [HR] 0.56; 95% CI: 0.36-0.90; p=0.014 (10.0 vs 4.8 months). Median PFS was 6.8 vs 3.4 months, (HR 0.44, 95% CI 0.31-0.63, P<0.001). Median OS had no significant difference between the arms (18.0 vs 20.5 months, HR 0.93, 95%CI 0.60-1.44, P=0.734). Intracranial ORR was significantly improved with icotinib than WBI+Chemo (67.1% vs 40.9%; p<0.001); Overall ORR was 55.0% vs 11.1% (P<0.001). Grade ≥3 AEs assessed by the investigators were reported in 8.2% (N=7) of patients treated with icotinib and 26.2% (N=28) treated with WBI+Chemo. Most common causally related AEs in the icotinib arm were increased liver transaminase & rash; in the WBI+Chemo arm were hematologic toxicity.

      Conclusion:
      Icotinib demonstrated superior iPFS, PFS and ORR over WBI+Chemo in EGFR mutant advanced NSCLC with brain M, and well-tolerated safety profile. Icotinib would be a treatment option for EGFR mutant patients with brain M (NCT01724801).

      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.

  • +

    SC17 - Lung Cancer: A Global Cancer with Different Regional Challenges (ID 341)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Regional Aspects/Health Policy/Public Health
    • Presentations: 1
    • +

      SC17.02 - Lung Cancer in China: Challenges and Perspectives (ID 6667)

      14:20 - 15:50  |  Author(s): L. Zhang

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Lung cancer is still the leading cause of cancer death in China. The estimated new lung cancer cases and deaths were 733,300 and 610,200 in 2015, respectively. Non-small cell lung cancer (NSCLC) remains the predominant form of the disease in China, with majority of patients being diagnosed at advanced stages. Thus this presentation will focus on advanced stage NSCLC. Current treatment strategy The current treatment algorithm for wild-type non-squamous and squamous NSCLC were shown in Figure 1 and 2, respectively. Figure 1 Figure 1. Treatment algorithm for non-squamous NSCLC (wild-type) Figure 2 Figure 2. Treatment algorithm for advanced squamous NSCLC For patients with activating EGFR mutations, EGFR-TKIs therapy will be used as front-line therapy. Commercial available EGFR-TKIs in China include Gefitinib, Erlotinib and Icotinib. For patients harbouring an ALK rearrangement, crizotinib will also be considered as first-line treatment. When failed from EGFR-TKIs or ALK-Inhibitor therapy, patients will be treated according to clinical model of disease progression. For patients with asymptomatic progression, continuing EGFR-TKIs or ALK-Inhibitor is recommended. For patients with local progression, EGFR-TKIs or ALK-Inhibitor will also be continued with additional local therapy such as whole brain radiation. However, for patients with aggressive progression, EGFR-TKIs or ALK-Inhibitor will be substituted by chemotherapy. Unfortunately, it is difficult to overcome drug resistance according to molecular mechanism because novel agents such as Osimertinib and Alectinib haven’t been approved by Chinese FDA. Challenge and perspective 1. Genetic alterations assays Genetic alterations are frequent in Chinese NSCLC patients. According to PIONEER study (NCT01185314), which is a prospective molecular epidemiology study in newly diagnosed advanced lung adenocarcinoma, the EGFR active mutation rate is 50.2% in Chinese patient population. The incidence of EGFR mutations in patients who never smoked can be as high as 59.6%. ALK rearrangement is also common in this patient population. In a large cross-sectional study enrolled 1160 NSCLC patients, the incidence of ALK rearrangements is 8.1%. Noteworthy, 44% of patients younger than 30 years old harbor ALK rearrangements. However, genetic alterations test rate used to be low in China. According to a large national survey, the EGFR mutation test rate was only 9.6% in 2011. However, as the turnover time shortens, the testing fee decreases, and ctDNA testing becomes available, the EGFR/ALK assays have turned into routine practice in China. Moreover, NGS platforms detecting panels of mutations are commonly used in some leading centers now. 2. Novel agent availability There is severe delay in the approval for novel agents by Chinese FDA. For instance, Bevacizumab was approved by FDA for treatment of NSCLC in 2006, while it was approved by Chinese FDA 9 years later. To improve availability of novel agents, Chinese oncologists are active in participation in international multi-center clinical trials. In addition, more and more innovative drugs have been developed by domestic pharma industry and entered clinical trials (Table 1). Moreover, Chinese FDA makes new policies to encourage innovative drugs and accelerating new drug application.

      Agent ID Classification Indication Phase
      Avitinib Mutation selected EGFR-TKI EGFR T790M Mutation Phase I
      Apatinib VEGFR-TKI Nonsquamous NSCLC in 3L Phase III
      Famitinib VEGFR-TKI Nonsquamous NSCLC in 3L Phase III
      Theliatinib EGFR inhibitor EGFR amplification Phase I
      Volitinib c-MET inhibitor c-MET amplification Phase I
      SHR-1210 PD-1 antibody NSCLC in 2/3L Phase I
      Table 1. Innovative drugs from China in clinical trials 3. Lung cancer prevention The incidence rate of lung cancer remains high in China between 2000 and 2011. Factors that have contributed to this issue include tobacco smoking and air pollution. 50% adult Chinese men were current smokers in 2010. In addition, smoking rates in adolescents and young adults are still rising in China. To reduce tobacco use in China, the government enact a strict smoking control law in Beijing in June 2015. However, the air pollution is still a severe problem and needs to be improved urgently. 4. Economic burden There are several factors which have contributed to the heavy economic burden of lung cancer patients in China. First, the residents’ income is still low in China. In 2015, per capita disposable income (one year) was only $3300. Second, the cost of anti-cancer drugs is very high (Crizotinib/cycle $8500, Gefitinib/cycle $2200, Pemetrexed/cycle $3000, and Bevacizumab/cycle $4500). Moreover, only 20% of whole medical expense can be covered by insurance, and majority of targeted drugs can’t be covered.





      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.