Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

O.S. Breathnach



Author of

  • +

    P1.21 - Poster Session 1 - Diagnosis and Staging (ID 169)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
    • +

      P1.21-004 - Profiling the clinical and diagnostic pathway of Epidermal Growth Factor Receptor (EGFR) mutant Non-Small Cell Lung Cancer (NSCLC) in Ireland (ID 1455)

      09:30 - 09:30  |  Author(s): O.S. Breathnach

      • Abstract

      Background
      The presence of an EGFR mutation in NSCLC provides prognostic and therapeutic information for patients and clinicians. This study investigates the clinical behaviour of EGFR mutant (MT) versus EGFR wild-type (WT) NSCLC in an Irish cohort of patients. Differences in the pattern of presentation, metastasis and diagnostic methods between patients with EGFR-MT and WT tumours are poorly characterised. In this retrospective study, we investigated these parameters, variations in EGFR mutation type and resultant impact on overall survival (OS).

      Methods
      Patients with EGFR-MT NSCLC were identified from a National Multi-Institutional database. Patient demographics, diagnostic and clinical data were collected by review of medical records. From the database, EGFR-WT controls matched for age, gender and stage were identified and used as a comparator group. Fisher’s exact and Mann-Whitney tests were used to compare variables between groups. Cox model was used to examine the effect of mutation type on OS.

      Results
      We identified 416 patients with NSCLC. Forty (10%) patients had EGFR-MT positive tumours, of which data were available on 35 (87%) patients. Among patients with EGFR-MT tumours, median age was 64 (range 35-89), 29 (83%) were female, 34 (97%) patients had adenocarcinoma, and 1 (3%) patient had adenosquamous carcinoma. Twelve (34%) patients had resected disease, and 23 (66%) had metastatic disease. At median follow up of 12.8 months, 3 (25%) patients with localised EGFR-MT disease recurred, 0 (0%) of EGFR-WT recurred. There were no significant differences in the pattern of disease between EGFR MT and WT in terms of central/peripheral localisation of primary lesion, or sites of metastasis such as the lung, liver, adrenal gland, bone or brain (p=1.0). Patients with EGFR-MT disease were more likely to be diagnosed via transbronchial biopsy (n=16, 47%) than EGFR-WT (n= 4, 11% p<0.01.) Patients with EGFR-WT disease were more likely to be diagnosed via endobronchial ultrasound/fine needle aspiration (FNA) (n= 21, 58%. p<0.01.) Among those with EGFR-MT disease, 19 (54%) patients had tumours which harboured Exon 19 deletions, and 6 (17%) harboured L858R mutations. The remaining mutations comprised L861Q, V689M and deletions in Exons 18, 20 and 21. Among patients with stage IV disease at diagnosis, the median OS was 20.9 months and 7.3 months for EGFR-MT and EGFR-WT disease respectively (p=0.16.) The median OS for patients who underwent resection was not reached in either group.

      Conclusion
      There were no significant differences in patterns of presentation and metastasis between patients with EGFR-MT and WT tumours in this cohort. Patients with EGFR mutations were more likely to be detected by transbronchial biopsy compared to patients with WT disease, who were diagnosed more commonly by FNA. Possible explanations for this include institutional preferences or ease of tissue acquisition. In this cohort, the most common mutations in EGFR were Exon 19 deletion or L858R. The likelihood of mutation detection might be improved with the inclusion of a full EGFR mutational analysis.

  • +

    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P3.11-042 - Molecular Inequality in the Treatment of Non-Small Cell Lung Cancer (NSCLC) and Implications for Clinical Trials (ID 2831)

      09:30 - 09:30  |  Author(s): O.S. Breathnach

      • Abstract

      Background
      Activating mutations (MT) in the epidermal growth factor receptor (EGFR) gene are found in approximately 10-20% of patients with NSCLC. Guidelines recommend therapy with EGFR tyrosine kinase inhibitors (TKI’s) in these patients, and in patients with EGFR Wild type (WT) tumours beyond second line. Clinical trials have focussed on optimising the management of patients with an actionable target. The real-world management of patients with EGFR MT’s and clinical trial recruitment has yet to be explored. This retrospective study investigated treatment patterns in an Irish cohort of patients with non-squamous NSCLC, stratified by EGFR-MT status.

      Methods
      Patients with EGFR-MT positive tumours were identified from a National Multi-Institutional database. Patients with EGFR-WT tumours matched for age, stage and gender were identified. Treatment data including receipt of chemotherapy, EGFR TKI, and clinical trial participation were collected. Fisher’s exact and Mann-Whitney tests were used to compare variables. Cox model was used to examine the influence of treatment variables on overall survival (OS.) To ascertain the milieu of clinical trials applicable to this cohort, www.clinicaltrials.gov was searched for all phase III interventional studies in NSCLC between 1/1/2010 and 31/5/2013. Trial characteristics were summarized.

      Results
      We identified 416 patients with NSCLC. Forty (10%) patients had tumours with EGFR MT’s, of which data were available on 35 (87%) patients. Twelve (34%) patients had resected disease, and 23 (66%) had metastatic disease. Nineteen (82%) EGFR-MT positive patients with metastatic disease received first line systemic therapy, 12 (63%) receiving EGFR TKI (p=0.52.) Fifteen (65%) patients with EGFR-WT tumours received first line chemotherapy. The median number of lines of treatment was 1 (range: 0 – 4; 30% >1 line) for patients with EGFR-MT’s and 1 (range: 0 – 3; 13% >1 line) for EGFR-WT (p<0.01.) Receipt of second, third and fourth line therapy was 26%, 13% and 4.3% for EGFR-MT positive patients respectively, and 8.6%, 4.3% and 0% respectively in EGFR-WT (p<0.01.) Six (24%) patients with an EGFR MT and 0 (0%) with EGFR-WT participated in clinical trials (p<0.01.) Significant benefits were seen for 1) receipt of 1 line of treatment vs. 0 (HR=0.2, 95% CI=0.08 – 0.18, p=0.03) or 2) >1 line of treatment vs. 0 (HR=0.10, 95% CI= 0.01- 0.46, p< 0.01) Twenty-four phase III trials in advanced NSCLC were identified over the study period. The most commonly investigated agents were TKI's - 10 (42%) and monoclonal antibodies – 6 (25%). Ten (42%) trials required the presence of a driver mutation for eligibility, and 13 (54%) trials were in second line or beyond.

      Conclusion
      In Irish patients with NSCLC the incidence of EGFR MT’s is comparable to other European populations. Our real-world experience demonstrates that patients with EGFR MT’s tend to receive more lines of therapy and have a higher rate of clinical trials participation, reflecting the portfolio of currently available clinical trials. While trials should strive to optimise treatment for EGFR-MT positive NSCLC, the thoracic oncology community should consider that biological heterogeneity can lead to inequalities in clinical trial development and subsequent treatment.