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Junling Li



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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/23/2018, 07:30 - 11:15, Room 202 BD
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      JCSE01.10 - A Ph3 Study of Niraparib as Maintenance Therapy in 1L Platinum Responsive Extensive Disease Small Cell Lung Cancer Patients (Now Available) (ID 11679)

      10:25 - 10:35  |  Author(s): Junling Li

      • Abstract
      • Presentation
      • Slides

      Background
      Small cell lung cancer (SCLC) accounts for 15% of lung cancer, characterized by early dissemination and rapid development of chemo-resistant disease after platinum response (60-80%). Less than 2% of extensive disease SCLC (ED-SCLC) patients survive 5 years. The bi-allelic loss or inactivation of TP53 and RB1 is common in SCLC, the poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA damage repair enzyme, is highly expressed in SCLC, and SCLC is sensitive to platinum based chemotherapy, suggesting that the defect in DNA damage repair pathways plays an important role in SCLC. ZL2306/ Niraparib is a highly selective PARP-1/2 inhibitor which was exclusively licensed for development in China by Zai Laboratory from TESARO. In SCLC PDX model, niraparib demonstrated anti-tumor activities as monotherapy. In addition, niraparib demonstrated promising tumor growth inhibition in maintenance post platinum treatment in platinum sensitive SCLC PDX models. Clinically, in phase III NOVA study, niraparib demonstrated clear clinical benefit as maintenance treatment by significantly extending progression free survival in all platinum-sensitive recurrent ovarian cancer patients regardless gBRCA or HRD status which led to the approval by FDA and EMA in ovarian cancer. It is suggested that niraparib maintenance therapy could provide potential clinical benefit in platinum responsive SCLC. ZL-2306-005 is a randomized double-blind multi-center phase 3 study to evaluate the efficacy and safety of niraparib versus placebo as maintenance therapy in ED-SCLC patients who have had responses to platinum based chemotherapy.Approximately 590 Chinese patients with histologically or cytologically confirmed ED-SCLC who have achieved either complete response or partial response to their platinum based chemotherapy to their newly diagnosed disease will be randomized (2:1) to 2 groups, receiving either ZL-2306 or placebo in ZL-2306-005 study. Patients need to complete 4 cycles of etoposide + cisplatin/ carboplatin. All patients will be stratified by gender, LDH level and history of prophylactic cranial irradiation. ZL-2306 will be started with 300mg PO QD for patients with a baseline body weight ≥77 kg and a baseline platelet count ≥150,000/μL, or 200 mg PO QD for patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL based on RADAR analysis in NOVA study. Patients will remain on treatment until disease progression or intolerable toxicity. The co-primary endpoints are PFS assessed by independent central radiologic review and OS; the secondary endpoints are PFS assessed by investigator, CFI, QoL, safety and tolerability.

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-101 - Survival Benefit of Sequential Therapy in ALK Positive Olioprogressive NSCLC Patients After Crizotinib Resistance (Now Available) (ID 13110)

      16:45 - 18:00  |  Author(s): Junling Li

      • Abstract
      • Slides

      Background

      Crizotinib is recommended as first-line standard therapy for advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC).Despite initial efficacy of crizotinib, patients ultimately acquired resistance, which leading to tumor progression within one year of crizotinib initiation. However,optimal sequential therapy option among patients with olioprogressive disease remains unknown.Therefore, this study aimed to explore which therapy pattern was advantageous for those patients with extracranial and intracranial metastasis.

      Method

      This retrospective single-center study enrolled 116 Chinese advanced ALK positive NSCLC patients resistant to prior crizotinib treatment,between Jan 2013 and Dec 2016.Based on the site of olioprogressive metastasis, patients were divided into two groups: extracranial (n=57,49.1%) and intracranial (n=59, 50.9%).Sequential therapies mainly included continuation of crizotinib with local therapeutics and next-generation ALK inhibitors. The primary end-point was median overall survival (OS) from the time of crizotinib resistance to death or last follow-up.

      Result

      Among 116 patients,45 patients (38.8%) had died. For extracranial group,26 patients continued crizotinib with local treatment (local radiotherapy or ablation therapy),31 received next-generation ALK inhibitor. Patients followed by next-generation ALK inhibitor beyond crizotinib resistance exhibited a longer OS of 27.6 months than crizotinib continuation with local therapy of 10.8months(p=0.009).Among intracranial group,36 patients continued crizotinib with local treatment including whole brain radiotherapy or stereotactic radiotherapy,23 were next-generation ALK inhibitors users. Continution of crizotinib with local therapy had a non-inferior OS than next-generation ALK inhibitors (28.9 month vs 32.8months, p=0.538) .

      Conclusion

      Next-generation ALK inhibitors had more survival benefit than continuation of crizotinib with local therapy for extracranial olioprogressive patients.While crizotinib continuation with local therapy might be a feasible strategy among patients with intracranial olioprogressive metastasis after crizotinib resistance.

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    P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 944)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.12-03 - A Prospective Study of Apatinib in Advanced Small Cell Lung Cancer Patients Failed from Two or More Lines of Chemotherapy (Now Available) (ID 13140)

      16:45 - 18:00  |  Author(s): Junling Li

      • Abstract
      • Slides

      Background

      Small lung cancer (SCLC), a highly malignant neoplastic, chemoresponsive disease. For SCLC patients who with worsening status after second-line treatment, there is currently no affirmative and widely accepted chemotherapy regimen. Apatinib is a novel oral multi-target small-molecule TKI mainly targeting the intracellular ATP-binding domain of VEGFR-2, which has a significant effect of anti-angiogenesis to suppress the growth of tumors. This study evaluated the efficacy and safety of Apatinib in SCLC patients who failed from second- or further-line chemotherapy.

      Method

      Data was collected from the files of patients treated with Apatinib 500mg qd who diagnosed with advanced SCLC and failed from second or more lines of chemotherapy. Efficacy assessed after one cycles (4 weeks), then every two cycles (8 weeks) once again. The primary endpoint was PFS and the tumor response was determined according to the RECIST 1.1. PFS were graphed by Kaplan-Meier curves of progression-free survival. AEs were also evaluated and toxicity grade was determined based on CTCAE 4.0.

      Result

      22 patients were enrolled from November 10, 2016 to April 18, 2018, the number of patients that can be evaluated is 19. One patients obtained partial response, and 15 obtained stable disease, representing a DCR of 84.11%. Median PFS was 140 days (95% confidence interval [CI] 94.84–185.16). Although only one patient showed PR, all the patients’ target lesions were reduced. A total of 46 AEs were reported during the trial, grade 3-4 AEs were hypertension (9.09%), leukopenia (4.55%) and proteinuria (4.55%) which most could be relieved by dose reduction. figure 1..jpg

      Conclusion

      In conclusion, Apatinib has a certain therapeutic effect in patients with advanced SCLC (third- or further-line). To further investigate the role of Apatinib in advanced SCLC patients, large sample and additional clinical trials are needed.

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-18 - Exploring the Resistance Mechanism of Osimertinib and Monitoring the Treatment Response Using Plasma ctDNA in Chinese NSCLC Patients (Now Available) (ID 13297)

      16:45 - 18:00  |  Author(s): Junling Li

      • Abstract
      • Slides

      Background

      Osimertinib (AZD9291; Tagrisso) is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) known to be effective for patients harboring the EGFR-T790M variant, which is accounts for more than half of the acquired resistance mechanisms to the first generation EGFR-TKIs. However, limited osimertinib resistance-mechanism was reported. Study on potential osimertinib-resistance mechanisms in advanced NSCLC is necessary.

      Method

      This study enrolled eight T790M-positive (tissue validated) patients, treated with osimertinib after first generation EGFR-TKI (Erlotinib, Gefitinib, Icotinib) resistance and progressed rapidly. Serial plasma samples were collected until disease progressed. Plasma DNA was extracted and sequenced by target-capture deep sequencing of 1021 previously annotated genes related to solid tumors. Clonal EGFR T790M mutation was defined if mutation was in the cluster with the highest mean variated allele frequency with PyClone, and otherwise subclonal EGFR T790M mutation. Molecular tumor burden index (mTBI) was calculated with the mean variant allele frequency of mutations in trunk clonal population.

      Result

      The median progression-free survival (PFS) of these eight rapidly-progressed patients was 3.82 months [95% CI 2.05-5.01] .Targeted capture sequencing of pretreatment ctDNA showed all of the eight patients (100%) were EGFR-positive (Exon19del [n=6] and L858R [n=2]), and seven patients (88%) harbored EGFR T790M mutation, except for the only one patient (P006) who showed an extremely low level of ctDNA. During the Osimertinib treatment, five patients (63%) had osimertinib resistance-related mutations: EGFR C797S (in cis position), G724S, KRAS G12D, PIK3CA E542K, EGFR amplification, and ERBB2 amplification. Among them, two patients had more than one resistance mechanisms: patient P034 had EGFR G724S, KRAS G12D and EGFR amplification, simultaneously; patient P013 had amplification in both EGFR and ERBB2. Other potential resistance mechanisms were identified including EGFR T751I and K754E mutations in P002 and ERBB2 S603 in P013. Notably, the only one patient (P004) who had not been detected to have any known osimertinib resistance mechanism but progressed in 3 months, was demonstrated to harbor a subclonal EGFR T790M mutation by analysis of ctDNA clonal structure. Serial ctDNA monitoring showed mTBI increased when disease progressed in 88% (7/8) patients, except P006, whose mutation were negative at second (stable disease) and third (progressed disease) therapeutic evaluations due to the extremely low level of ctDNA.

      Conclusion

      This study presented comprehensive the resistance mechanism of osimertinib progressed rapidly in ctDNA including multiple mechanisms co-occurred in same patient. Serial monitoring of plasma ctDNA may be a promising approach to explore resistance mechanism and monitored the treatment response of third generation EGFR-TKI.

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-109 - Treatment Duration—­A More Reasonable Definition to Evaluate the Efficacy of Crizotinib in ALK Positive Advanced NSCLC (Now Available) (ID 13216)

      16:45 - 18:00  |  Author(s): Junling Li

      • Abstract
      • Slides

      Background

      Crizotinib has demonstrated its superior efficacy in ALK positive NSCLC patients when used as first-line regimen, with a median overall survival (OS) of more than 4 years, whereas a median progression-free survival (PFS) of only 10.9 months. Patients who continued crizotinib beyond progressive disease (CBPD) could still obtain additional survival benefits of 6-8 months after disease progression. In terms of that, PFS, the frequently used primary endpoint in clinical trials, may not be able to provide accurate information on impact of this intervention in multiple lines therapy. Here we proposed “treatment duration” as an intermediate clinical endpoint between PFS and OS that further define efficacy of crizotinib in multiple lines of treatment and reported the exploratory data in a real-world cohort.

      Method

      We retrospectively enrolled 150 ALK positive NSCLC patients who had acquired crizotinib resistance from Aug 2011 to May 2017. The median PFS of crizotinib and median OS (from crizotinib initiation) were analyzed. Treatment duration of crizotinib, the time from crizotinib initiation to discontinuation, was also calculated.

      Result

      The median PFS of crizotinib in the 150 ALK positive advanced NSCLC patients was 14.4 months (95% CI: 11.3-17.4). Overall, 58 patients (38%) continued CBPD and the median post-progression PFS was 10.4 months, resulting in a median treatment duration of crizotinib in the total cohort of 20.2 months (95% CI: 14.3-26.0). And median OS was 30.1months (95% CI: 21.3-38.8). 77 (51%) patients who received crizotinib as first-line therapy exhibited both longer median PFS (17.7 months, 95% CI: 12.5-22.9; vs. 12.2months, 95% CI: 7.6-16.8) and median OS (35.2 months, 95% CI: 23.2-47.1; vs. 25.4 months, 95% CI: 14.4-36.3) compared to those selected crizotinib as second- line and above therapy. The treatment duration among them were 23.1 months (95% CI: 14.7-31.4) and 18.9 months (95% CI: 11.4-26.3), respectively.

      Conclusion

      Crizotinib showed superior efficacy in ALK positive NSCLC patients. Treatment duration may be more reasonable to define the efficacy of crizotinib in multiple lines therapy of ALK positive NSCLC.

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    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.13-04 - Outcomes of ALK-Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Crizotinib: A Multicenter Cohort Retrospective Study. (Now Available) (ID 13304)

      16:45 - 18:00  |  Author(s): Junling Li

      • Abstract
      • Slides

      Background

      Crizotinib has demonstrated promising efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in clinical trials. However, there is lack of multicenter real-world data summary with large cohort of patients, especially in China. We conducted this multicenter and retrospective study to assess the outcomes of crizotinib in, to our knowledge, the largest cohort of patients with ALK-positive advanced NSCLC.

      Method

      We reviewed medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at five cancer centers in China from January 2013 to November 2017. Clinical data were collected from crizotinib initiation to RECIST-defined progressive disease (PD), and post-PD systemic treatment outcomes were also analyzed.

      Result

      A total of 428 eligible ALK-positive NSCLC patients were enrolled. Among them, 273 (63.8%) patients received crizotinib as first-line treatment. The median progression-free survival (PFS) and overall survival (OS) from crizotinib initiation were 14.4 months (95%CI: 12.4-16.4) and 53.4 months (95% CI: 33.7-73.1) respectively. In the subgroup analysis, patients received crizotinib as first-line treatment showed a higher disease control rate (DCR) and longer median OS with statistical significance compared with second-/ further line crizotinib treatment (94.8%, not estimated vs. 89.0%, 40.5 months, respectively). For 261 patients with RECIST-defined PD, multivariate COX analysis revealed that patients who received first-line crizotinib (P=0.013), continued crizotinib beyond progressive disease (CBPD) (P=0.011) and received next-generation ALKis after crizotinib failure (P<0.001) were associated with improved survival both from crizotinib progression and from the first crizotinib dose.

      Conclusion

      This study demonstrated the clinically meaningful benefit of crizotinib treatment in the largest cohort of Chinese ALK positive NSCLC patients. CBPD and next-generation ALK TKI treatment may provide survival improvement after RECIST-defined progression on crizotinib.

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      P2.13-05 - Real-World Clinical Benefit of Continuing Crizotinib Beyond Progression Disease (CBPD) in Patients with Advanced ALK-Positive NSCLC. (Now Available) (ID 13353)

      16:45 - 18:00  |  Author(s): Junling Li

      • Abstract
      • Slides

      Background

      Most ALK-positive NSCLC patients treated with crizotinib would ultimately develop progressive disease (PD), and continuing crizotinib beyond initial PD (CBPD) may be potentially beneficial. We aim to evaluate the survival outcomes of patients with crizotinib resistance in real-world setting and to explore the clinical efficacy of continuing CBPD treatment.

      Method

      A total of 261 ALK-positive NSCLC patients treated with crizotinib experienced RECIST-defined PD and were included in this multi-center retrospective analysis. Clinicopathologic characteristics, progressive pattern, post-PD treatment and overall survival (OS) were compared between patients continuing CBPD and those not.

      Result

      140 patients who continued crizotinib after disease progression were allocated to CBPD group and others were non-CBPD group. Two-sided Chi-square test showed that patients who never smoked (P=0.047), with ECOG 0-1(P=0.001), isolated intracranial progression (P<0.001) and <median PFS of initial crizotinib (P=0.002) were more likely in the CBPD group. At the analysis, 84 patients had re-PD and the median duration of crizotinib treatment post-PD was 6.8 months (95%CI: 3.639-9.869). The median OS for the overall population from the time of PD (post-PD OS) was 15.3 months (95%CI: 11.376-19.181), and was significantly longer in CBPD patients than non-CBPDs (24.1 months vs. 8.5 months, 95% CI: 0.326-0.669, HR 0.467, P<0.001). Furthermore, next-generation ALK inhibitors (ALKis) following crizotinib failure was associated with improved post-PD OS (24.9 months vs. 10.7 months, 95% CI: 0.307-0.686, HR 0.459, P<0.001).

      Conclusion

      Continuing CBPD treatment after crizotinib resistance favorably impact survival outcomes of advanced ALK-positive NSCLC patients in the real-world. Next-generation ALKis may provide survival improvement, but comparative studies between different subsequent treatment options after PD on crizotinib are still needed.

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-103 - Efficacy of Crizotinib in Chinese Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Multicenter Retrospective Study (ID 12578)

      12:00 - 13:30  |  Author(s): Junling Li

      • Abstract
      • Slides

      Background

      Brain metastasis in advanced non-small cell lung cancer (NSCLC) patients is often considered as a terminal stage. Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) for ALK-rearranged NSCLC patients. Herein we conducted a multi-center retrospective study to explore how crizotinib affects the control of brain metastasis and survival outcomes among advanced ALK-rearranged NSCLC patients with brain metastasis in Chinese population.

      Method

      We reviewed medical records of 484 unselected ALK-positive NSCLC patients treated with crizotinib at five cancer centers in China from January 2013 to November 2017. Patients developing brain metastasis either before or during the crizotinib treatment were enrolled. Survival outcomes were analyzed with Kaplan-Meier method and prognostic factors were analyzed with multivariate COX analysis.

      Result

      A total of 174 patients were enrolled into this study, of whom 95 patients had baseline brain metastasis and 79 patients developed brain metastasis during crizotinib treatment. Among patients with baseline brain metastasis, the median intracranial progression-free survival (PFS) was 15.34 months [95% confidence interval (CI): 10.62-20.07] and median overall survival (OS) was 53.38 months (95%CI: 30.58-76.17). The intracranial objective response rate (ORR) was 17.1%, and the intracranial disease control rate (DCR) was 88.6%. Multivariate COX analysis revealed that patients receiving first-line crizotinib [>first-line vs. first-line, hazard ratio (HR): 2.44, 95%CI: 1.05-5.68, p=0.038], withtout intracranial progression during crizotinib treatment (with vs. without intracranial progression, HR: 18.68, 95%CI: 2.43-143.31, p=0.005) were associated with better OS, while age, sex, number of brain lesions, and operation/radiation therapy for brain metastasis were not significantly associated with OS. Among patients developing brain metastasis during crizotinib treatment, the median OS was 35.64 months (95%CI: not reached). Multivariate COX analysis revealed that brain progression only (brain progression only vs. both brain and extracranial progression, HR: 0.23, 95%CI: 0.08-0.71, p=0.011) was associated with better OS, while age, sex, line of crizotinib treatment, treatment after progression and operation/radiation therapy for brain metastasis were not significantly associated with OS.

      Conclusion

      Advanced ALK-rearranged NSCLC patients with baseline brain metastasis could still benefit from crizotinib treatment. However, brain progression during crizotinib treatment may be associated with worse survival outcomes.

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