Author of

• 25724

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  MA02 - Improving Outcomes for Patients with Lung Cancer (ID 895)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 10:30 - 12:00, Room 201 BD

  • 25726

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    MA02.06 - A Randomized, Double-Blind, Placebo-Controlled Trial of Chemotherapy Combined with Yangzheng Xiaoji in Advanced NSCLC (ID 13562)

    11:05 - 11:10  |  Presenting Author(s): Ligang Xing
    • Abstract
    • Presentation
    • Slides

    Background
    

    Yangzheng Xiaoji (YZXJ) is a Chinese medicine formulation made of 16 herbs and used in patients with solid cancers. The aim of this randomized, double-blind and placebo-controlled multi-center trial (YANG-1，ClinicalTrials.gov registration No. NCT02195453) is to evaluate the impact of Yangzheng Xiaoji capsule on the quality of life (QoL) and treatment-related side effects in patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Patients with advanced NSCLC and with Eastern Cooperative Oncology Group performance status 0 to 1, who receive first-line chemotherapy (gemcitabine or pemetrexed and cisplatin), were randomized (1:1) to Yangzheng Xiaoji (YZXJ) or placebo combined with chemotherapy. The primary endpoint was QoL (Functional Assessment of Cancer Therapy-Lung (FACT-L) and Lung Cancer Symptom Scale (LCSS)) after two or four cycles of chemotherapy. The second endpoints included overall response rate, progression free survival and toxicity.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Between 10/2014 and 4/2017, the trial enrolled and randomized 504 patients from 25 centers in China. 397 patients received at least two cycles of chemotherapy and were included for final analysis. Baseline characteristics, including FACT-L and LCSS scores, were well balanced between two groups. The mean FACT-L scores were significantly changed in both groups from the baseline to that after chemotherapy (97.58 increase to 100.89 in YZXJ/chemotherapy arm, P<0.001; 93.83 decrease to 97.93 in placebo arm, P<0.001). The mean score of LCSS from baseline was significantly changed in YZXJ/chemotherapy groups(25.84 decrease to 22.31, P<0.001), but there was no statistical difference in the placebo group(25.59 vs. 26.45, P=0.136). The YZXJ/chemotherapy arm had a better QoL than the placebo/chemotherapy arm (FACT-L, 3.30 vs. -4.09; P<0.001) as well as improved lung cancer symptoms compared with placebo (LCSS, -3.53 vs. -0.86; P<0.001). There was no statistical difference in chemotherapy completion rate, ORR and PFS between two groups. The most common adverse events were bone marrow toxicity (70.92% vs. 67.59%) and gastrointestinal reaction (34.66% vs. 63.24%) (YZXJ vs. Placebo, P=0.441 and P<0.001, respectively). The rate of fatigue was significantly lower in YZXJ group than placebo group (4.38% vs. 30.04%, P<0.001).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    For patients with advanced NSCLC who received platinum-based chemotherapy, Yangzheng Xiaoji Capsule significantly improved the quality of life and symptoms, especially fatigue and gastrointestinal reaction.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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• 25933

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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
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 27880

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    P1.13-25 - Efficacy and Safety of Osimertinib in EGFR T790M-Positive Advanced NSCLC Patients with Brain Metastases (APOLLO Study) (ID 13178)

    16:45 - 18:00  |  Presenting Author(s): Ligang Xing
    • Abstract
    • Slides

    Background
    

    Osimertinib has demonstrated promising efficacy in T790M-positive NSCLC patients with central nervous system (CNS) metastases, but there is limited data on Chinese patients. We aim to investigate the efficacy and safety of osimertinib in T790M-positive advanced NSCLC patients with brain metastases and to explore the dynamic genetic changes as well as drug penetration in CNS with paired cerebrospinal fluid (CSF) and plasma samples.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    In this single arm, multi-center, prospective trial (NCT2972333), patients with confirmed EGFR T790M positive by Cobas, advanced NSCLC with brain metastases, who had progressed following first-generation EGFR-TKI treatment, received osimertinib 80 mg qd. The primary endpoint was overall progression free survival (PFSo). Paired CSF-plasma samples were collected at baseline, 6 weeks after treatment and disease progression and analyzed by NGS.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Thirty-eight eligible patients were enrolled and 12 paired CSF-plasma samples were collected. Baseline characteristics and efficacy results are summarized in Table 1. Median PFSo (60% maturity, 23/38) was 8.4 months (95% CI 5.8-11.0). Adverse events of grade 3 or higher were reported in 39.5% patients. Analyzed in 12 paired samples, the median CSF penetration rate of osimertinib was 31.7% (range 19.8-57.7%), with a median CSF concentration of 10.83nM (range 5.2-30.3nM). T790M mutation was detected in 83% (10/12) of plasma and 17% (2/12) of CSF samples at baseline, with a concordance rate of 8.3% (1/12). Median PFSo was prolonged in patients with EGFR sensitizing mutation clearance at week 6 compared with those with persisting EGFR mutations (not reached vs 2.83 months; HR 0.09, 95% CI 0.02-0.54; p<0.01).

    Table 1. Baseline characteristics and efficacy

    Patients characteristics	N=38
    Age, median (range), years	63 (38-74)
    CNS metastases, No (%): brain metastases (BM) / leptomeningeal metastases (LM) / other	35 (92.1%) / 2 (5.3%) / 1 (2.6%)
    Histology, No (%): adenocarcinoma	38 (100%)
    EGFR mutations, No (%): T790M with Ex19del / L858R	22(57.9%) /16 (42.1%)
    Sample type for T790M confirmation No (%): Blood / Tissue	27 (71.1%) / 11 (28.9%)
    Lines of anti-tumor therapy, No (%): 1 / 2 / ≥3	13 (34.2%) / 3 (7.9%) / 22 (57.9%)
    Efficacy	Overall	Extracranial	Intracranial
    Median PFS (months, 95% CI)	8.4 (5.8, 11.0)	10.2 (7.5, 14.0)	10.9 (6.1, NA)
    Objective response rate (ORR)	42.4%(14/33)	39.4%(13/33)	71.9%(23/32)
    Disease control rate (DCR)	90.9%(30/33)	90.9%(30/33)	96.9%(31/32)
    Median Duration of Response (DoR) (months, 95% CI)	8.1 (3.4, NA)	11.1 (5.6, 11.1)	8.3 (5.8, NA)

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Osimertinib demonstrated promising efficacy, good blood brain barrier penetration and manageable tolerability in EGFR T790M-positive Chinese advanced NSCLC patients with brain metastases. NGS analysis revealed genetic heterogeneity between plasma and CSF samples and longitudinal genetic analysis may be beneficial to predict the efficacy of osimertinib.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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