Author of

• 25950

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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: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 27184

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    P2.13-11 - EGFR Amplification and Sensitizing Mutations Correlates with Survival from Erlotinib in Lung Adenocarcinoma Patients (MutP-CLICAP¶) (ID 14305)

    16:45 - 18:00  |  Author(s): Leonardo Rojas
    • Abstract

    Background
    

    Tumor heterogeneity causes different EGFR mutation abundances, and is believed to be responsible for varied progression-free survival (PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment. EGFR amplification and its common presence in EGFR mutant allele might be determined by the EGFR copy number variation. Examination of EGFR amplification status in EGFR mutant patients could predict the efficacy of EGFR-TKI treatment

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    72 lung ADC patients, who harbored EGFR activating mutations and received erlotinib as first line treatment, were examined for EGFR amplification by FISH. We analyzed the relationship between the EGFR mutational status and copy number profile with clinical outcomes including response rate, overall-survival (OS), and PFS.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Median age was 62-yo (r, 20-87 years), 53 patients were females (73%), and 89% had common mutations. Twenty-two (30.6%) samples with EGFR activating mutations were identified as having EGFR amplification. EGFR amplification was more frequent in patients with exon 19 deletion (p=0.05) and in those with better performance status (p=0.01). Patients with EGFR gene amplification had a significantly longer PFS than those without [(25.2 months, 95%CI 22.0-38.5) vs. (12.4 months, 95%CI 5.3-19.5); p=0.002] as well as better OS [(EGFR amplified 37.8 months, 95%CI 30.9-44.7) vs. (EGFR non-amplified 27.1 months, 95%CI 12.8-41.3); p=0.009]. EGFR amplification significantly influenced the response to erlotinib (p=0.0001).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    EGFR amplification occurs in one third of patients with lung ADC harboring EGFR activating mutations, and could serve as an indicator for better response and survival from EGFR-TKI treatment.

    6f8b794f3246b0c1e1780bb4d4d5dc53

• 25955

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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

  • 27362

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    P3.01-11 - Depression and Inflammation in Patients with EGFR-Mutated Non-Small Cell Lung Cancer (ID 14336)

    12:00 - 13:30  |  Author(s): Leonardo Rojas
    • Abstract

    Background
    

    Although depression appears to be associated with worse survival outcomes in cancer patients, the underlying mechanisms and basis of this association remain unknown. EGFR mutations have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, previous reports have described a positive association between this genotype and depression. This relationship could be at least partially explained by TNFa-mediated inflammation, which activates the hypothalamus-pituitary-adrenocortical (HPA) axis, leading to tryptophan depletion through the stimulation of indoleamine 2,3 dioxygenase.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    32 patients diagnosed with metastatic NSCLC with an EGFR mutation were enrolled and followed monthly. In all cases patients were evaluated using the Self-rating depression scale (SDS) and the Numeric Rating Scale (NRS) in order to obtain a detailed evaluation of the initial symptoms and a qualitative assessment of the state of depression. In parallel we measured TNFa levels in serum/plasma (MaxDiscovery™ Human TNF-α ELISA Test Kit) upon receipt of genotype report, 4 and 12 weeks after initiating the targeted therapy, and at the time of progression. We examined differences between patients with and without depression with respect to the TNFa, as well as impact on various outcomes.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Mean age was 58.9 years (+/- 12.4), 22 (68.8%) were women and 94% had an ECOG <2. Nineteen patients (59.4%) carried a del19, 8 (25%) had L858R, 2 (6.3%) L858R+T790M, 2 (6.3%) G719S and one patient had a del19+S768I (3.1%). Median follow-up was 15.4 months (95%CI 2.8-32.0), overall survival (OS) was 28.1 months (95%CI 25.5-30.6) and median progression-free survival (PFS) to first-line TKI was 13.1 months (95%CI 9.6-16.6).37.5% (n=12) of patients self-reported depression; in 25, 9.4 and 3.1% the clinical manifestations were mild (SDS 50-59; supportive psychotherapy), moderate (SDS 60-69; requirement of antidepressants) and severe (SDS 70 and above; required hospitalization). Depression was significantly associated with moderate-to-severe basal dyspnea (p=0.043), with brain metastases (p=0.003), and poor performance status (p=0.021). The average TNF at the time of genotype report was 12.2 pg/mL (SD±4.1), and was significantly higher in those who manifested depression (p=0.03). TNF levels increased 11% at 4 weeks and 75% at 12 weeks. Depression did not influence OS or first-line PFS.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Mild to moderate depression is prevalent in patients with lung cancer harboring EGFR mutations. As previously reported, TNFa levels are elevated in patients with lung cancer and depression, particularly in the first 12 weeks post-treatment, a finding attributable to inflammation.

    6f8b794f3246b0c1e1780bb4d4d5dc53