194P - KRAS status as predictive marker of response and time to progression in EGFR wild-type stage IV non-squamous non-small cell lung cancer (NSCLC) pati...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Presenter Manuel Domine
Authors M. Domine1, F. Rojo2, Y. Izarzugaza1, S. Zazo2, F. Lobo3, M. Fernandez Aceñero2, J. Madoz4, V. Casado1, G. Rubio1, J. Garcia Foncillas5
  • 1Oncology, Hospital Universitario. Fundacion Jimenez Diaz. Universidad Autónoma de Madrid, 28040 - Madrid/ES
  • 2Pathology, Hospital Universitario. Fundación Jimenez Diaz, 28040 - madrid/ES
  • 3Servicio De Oncologia, Hospital Universitario. Fundacion Jimenez Diaz. Universidad Autónoma de Madrid, 28040 - Madrid/ES
  • 4Pathology Department, Fundacion Jimenez Diaz, 28040 - Madrid/ES
  • 5Department Of Oncology, Hospital Universitario. Fundacion Jimenez Diaz. Universidad Autónoma de Madrid, 28040 - Madrid/ES

Abstract

Background

KRAS mutations are present in ∼30% of NSCLC patients and have been associated with upregulation of genes implicated in angiogenesis as vascular endothelial growth factor (VEGF). Bevacizumab (BVZ) is a recombinant monoclonal humanized antibody targeted against VEGF and added to carboplatin-paclitaxel chemotherapy has demonstrated to improve outcome in non-squamous NSCLC. The objective of this study was to analyze the impact of KRAS mutations in response rate (RR) and time to progression (TTP) in a cohort of patients homogeneously treated with BVZ in combination with platin-docetaxel compared with a control group of patients treated with same chemotherapy backbone.

Methods

EGFR wild-type patients treated with up to 6 cycles of carboplatin (AUC 5) or cisplatin (75mg/m2), docetaxel (75mg/m2) and BVZ (7.5mg/kg) on day 1, every 21 days. Patients with RR or stable disease continued maintenance BVZ (7.5 mg/kg) every 21 days until progression. Control group was treated with the same chemotherapy without BVZ. KRAS mutations at codons 12, 13 and 61 were analyzed by cobas KRAS Mutation Test (Roche) from DNA purified from diagnostic samples.

Results

30 patients were enrolled in the BVZ group: 24 male, 6 female; median age: 62 years; ECOG 1/2: 22/8; 27 adenocarcinoma and 3 undifferentiated large cell carcinoma. From them, 7 (23.3%) patients were KRAS mutated. 16 patients were enrolled in the control group: 14 male, 2 female; median age 58; ECOG 1/2: 9/7; 13 adenocarcinomas and 3 undifferentiated large cell carcinoma. From control group, 3 (18.8%) were KRAS mutated. BVZ therapy showed a significant improved efficacy in KRAS wild-type compared to mutated patients (RR: 88.9% vs 14.3%, p = 0.045; and TTP: 9.4 months vs 7.5 months, p = 0.033), but did not impact on overall survival (12.4 months vs 11.1 months, p= 0.780). These differences were not observed in control group. Moreover, in KRAS wild-type patients, the BVZ addition to therapy showed a significant improved efficacy compared to control group (RR: 88.9% vs 20%; p = 0.001).

Conclusions

KRAS wild-type status in wild-type EGFR stage IV non-squamous NSCLC might be associated with enhanced RR and TTP in BVZ-platin-docetaxel treated patients, suggesting a potential role as a predictive biomarker in this population.

Disclosure

All authors have declared no conflicts of interest.