LBA9_PR - Association between Tumor EGFR and KRas Mutation Status and Clinical Outcomes in NSCLC Patients Randomized to Sorafenib plus Best Supportive Care (B...

Date 29 September 2012
Event ESMO Congress 2012
Session Biomarkers in lung cancer
Topics Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Presenter Tony Mok
Authors T.S.K. Mok1, L. Paz-Ares2, Y. Wu3, S. Novello4, E. Juhász5, O. Aren6, Y. Sun7, V. Hirsh8, E.F. Smit9, C. Lathia10, T.J. Ong11, C. Pena10
  • 1Department Of Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, Shatin, Hong Kong/CN
  • 2Hospital Virgen del Rocio, 41013 - Seville/ES
  • 3Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN
  • 4Thoracic Oncology Unit, University of Turin, 10043 - Orbessano, Turin/IT
  • 5Pulmonology Department Xiv, Koranyi National Institute of TB and Pulmonology, 1529 - Budapest/HU
  • 6Oncologia Medica, Instituto Nacional de Cancer, 838-0455 - Santiago/CL
  • 7Cancer Hospital/institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing/CN
  • 8Royal Victoria Hospital, McGill University Health Centre, H3A 1A1 - Montreal/CA
  • 9Dept. Of Pulmonary Diseases, Vrije University Medical Centre (VUMC), NL-1081 HV - Amsterdam/NL
  • 10Clinical Sciences, Bayer HealthCare Pharmaceuticals, 07045 - Montville/US
  • 11Statistics, Bayer HealthCare Pharmaceuticals, 07045 - Montville/US



Background: Tumor EGFR and KRas mutations are both predictive and prognostic biomarkers in patients with advanced NSCLC. We analyzed the correlation between these biomarkers and treatment outcomes in a phase III trial of 3rd/4th line sorafenib in patients with NSCLC.

Methods: The global, randomized, placebo-controlled MISSION trial enrolled 703 patients with advanced relapsed/refractory NSCLC of predominantly non-squamous histology. The primary study endpoint was overall survival (OS). EGFR and KRas mutations were analyzed in archival tumor samples and in circulating tumor DNA isolated from plasma.

Results: Tumor and/or plasma mutation data were available from 347 patients (49%). EGFR and KRas mutations were detected in 89 (26%) and 68 (20%) patients, respectively, and were well balanced between treatment arms. Analysis of the interaction between EGFR mutation status and treatment effect on survival suggested that patients with EGFR mutations (mEGFR) benefitted from sorafenib, while those with wild-type EGFR (wtEGFR) did not (p=0.023). Median OS was two-fold longer in mEGFR patients receiving sorafenib versus placebo (423 vs 197 days, HR 0.48, p=0.002). There was no significant difference in OS between patients with wtEGFR receiving sorafenib or placebo (253 vs 256 days, HR 0.92, p=0.559). An interaction was also seen between EGFR mutation status and the sorafenib effect on PFS (p=0.015). Patients with mEGFR treated with sorafenib had better outcomes compared to placebo based on Cox regression analysis (HR 0.27, p<0.001; median PFS 83 vs 42 days) than patients with wtEGFR (HR 0.62, p<0.001; median PFS 82 vs 46 days). KRas mutation status was not predictive of sorafenib efficacy.

Conclusion: Post-hoc analyses of efficacy outcomes in MISSION suggest that advanced NSCLC patients with EGFR mutations may derive a survival benefit from receiving 3rd/4th line sorafenib. These results must be interpreted with caution due to the small, non-representative nature of the genetic biomarker subpopulation analyzed in this trial. Further prospective investigation may be warranted.