Author of

• 10583

  +

  P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10640

    +

    P1.06-057 - Incidence and significance of tumor EGFR and KRAS mutations in Greek metastatic non-small cell lung cancer patients treated with 1st line chemotherapy. (ID 3405)

    09:30 - 09:30  |  Author(s): V. Kotoula
    • Abstract

    Background
    KRAS mutations are reported in 20-25% of non-small cell lung cancer (NSCLC). Little is known about the prognostic/predictive role of KRAS in advanced NSCLC, with conflicting results among small studies, while recent evidence showed that they could predict for worse outcome in patients treated with platinum-based adjuvant chemotherapy. Evidence is also inconclusive on the prognostic role of EGFR mutations. Given that ethnicity may play a role on the mutational profiling of NSCLC, we report here on the first large scale mapping of NSCLC in Greek patients.

    Methods
    KRAS and EGFR genotypes were evaluated in 634 NSCLC patients with available clinical data, diagnosed from March 2000 to December 2012 (tissue blocks from the HeCOG tumor repositories). KRAS and EGFR mutations were associated with clinicopathological parameters (mutated vs. wild-type). Outcome comparisons were performed in 469 metastatic patients with available treatment data, following 1[st ]line chemotherapy without tyrosine kinase inhibitors.

    Results
    The majority of the patients were male (78%), current smokers (47%), with adenocarcinoma (AC) histology (68%). EGFR mutations were found in 14% and KRAS mutations in 15% of all histological types, while in AC they were 17% and 22%, respectively. Most EGFR mutations were classical (79%), while the most common KRAS mutations were p.G12C (35%), p.G12D (25%) and p.G12V (11%). Five tumors had concurrent EGFR and KRAS mutations. EGFR mutations were significantly associated with female gender, AC histology and non-smoking status, as previously described. KRAS mutations were associated with AC histology and younger age (<60). At a median follow-up of 39 months, EGFR status was prognostic for improved PFS (HR=0.52, 95% CI 0.35-0.78, p=0.001), in patients treated with 1[st] line chemotherapy and no TKIs, and OS (HR=0.64, 95% CI 0.43-0.95, p=0.028). KRAS mutations did not show any significant associations with OS or PFS, although a trend for worse outcome in KRAS mutated patients was observed. Furthermore, there was a significant difference in response to 1[st] line treatment according to KRAS status, with KRAS mutations associated with worse outcome (Clinical benefit, CR+PR+SD: 64.4% in wildtype vs 48.8 in mutant, and PD 23.4% in wildtypet vs 39.5% in mutant). No significant interaction between KRAS/EGFR status (EGFRmut vs. KRASmut vs. any wt) and platinum-based treatment was observed (p=0.975 for PFS and p=0.892 for OS).

    Conclusion
    EGFR and KRAS genotype incidences are presented for the first time in Greek metastatic NSCLC patients. In this setting, the presence of EGFR mutations shows prognostic significance in patients treated with 1[st] line chemotherapy, without TKIs, while the presence of KRAS mutations seems to adversely affect the response to 1[st] line chemotherapy.