O-0007 - Subgroup analyses in RAS mutant, BRAF mutant and “all wt” metastatic colorectal cancer patients treated with FOLFOXIRI plus bevacizumab (bev) or...

Date 27 June 2014
Event World GI 2014
Session Presentation of selected abstracts
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Presenter Chiara Cremolini
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors M. Ronzoni1, A. Zaniboni2, G. Tonini3, C. Valsuani4, S. Chiara5, C. Boni6, L. Marcucci7, F.V. Negri8, S. Vitello9, M. D'Amico10, C. Granetto11, G. Fontanini12, D. Tomcikova13, L. Boni14, A. Falcone15, G. Tomasello16
  • 1Dipartimento di Oncologia, Istituto Scientifico San Raffaele, Milano/IT
  • 2U.O. Oncologia Medica, Casa di Cura Poliambulanza, Brescia/IT
  • 3Università Campus Bio-Medico, Rome/IT
  • 4U.O. Oncologia Medica, Ospedale Versilia, Lido di Camaiore, Lucca/IT
  • 5U.O. Oncologia Medica, IRCSS Azienda Ospedaliero-Universitaria S. Martino-IST, Genova/IT
  • 6U.O. Oncologia Medica, Nuova Azienda Ospedaliera, Reggio Emilia/IT
  • 7U.O. Oncologia Medica, Azienda USL-5 Istituto Toscano Tumori, Pontedera/IT
  • 8Medical Oncology Unit, University Hospital of Parma, Parma/IT
  • 9U.O. Oncologia, Ospedale Sant'Elia, Caltanissetta/IT
  • 10S.C. Oncologia Medica E.O. Ospedali Galliera, Genova/IT
  • 11U.O. Oncologia Medica, Azienda Sanitaria Ospedaliera S. Croce e Carle, Cuneo/IT
  • 12Divisione di Anatomia Patologica, Dipartimento di Chirurgia, Università di Pisa, Pisa/IT
  • 13Istituto Toscano Tumori, Florence/IT
  • 14Clinical Trials Coordinating Center, Istituto Toscano Tumori, Firenze/IT
  • 15Oncologia Medica 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa/IT
  • 16Divisione di Medicina e Oncologia Medica, Azienda Istituti Ospitalieri di Cremona, Cremona/IT

Abstract

Introduction

Phase III TRIBE trial demonstrated that first-line FOLFOXIRI plus bev improved PFS and RECIST response and, at adjusted analyses, OS as compared to FOLFIRI plus bev as first-line treatment for metastatic colorectal cancer (mCRC) patients (pts). The prognostic and/or predictive effect to anti-EGFRs of RAS and BRAF mutation is well established. We conducted this post-hoc analysis in the TRIBE study in order to describe the predictive and prognostic effect of each molecular category.

Methods

Mutational analyses were centralized at the Coordinating Center. Mutations within KRAS and NRAS codon 12, 13 and 61 and BRAF codon 600 were analyzed by means of pyrosequencing in tumoral DNA extracted from primaries or metastases. Pts not bearing RAS or BRAF mutations were defined as “all wt”.

Results

Molecular results are available for 375 out of 508 randomized pts (73.8%). KRAS, NRAS and BRAF were found mutated (mut) in 198 (52.8%), 20 (5.3%) and 28 (7.5%) cases, respectively. All wt pts were 129 (34.4%). No significant interaction between RAS or BRAF status and treatment effect was reported in PFS or OS (see table). All wt pts treated with upfront FOLFOXIRI plus bev achieved median PFS and OS of 13.3 and 41.7 mos respectively. In terms of prognostic effect, as compared to all wt pts, BRAF mut had significantly shorter PFS (HR: 2.29 [1.49-3.52], p = 0.0002) and OS (HR: 3.31 [2.03-5.39], p < 0.0001) while for RAS mut no difference in PFS was detected (HR: 1.15 [0.91-1.45], p = 0.256), but OS was significantly shorter (HR: 1.48 [1.09-2.00], p = 0.012).

Conclusion

Benefit from FOLFOXIRI plus bev was independent of RAS and BRAF mutational status with a trend toward a larger benefit in BRAF mut, limited by small subgroup size. All wt pts treated with FOLFOXIRI plus bev achieved impressive PFS and OS results. Independently from the treatment received, RAS or BRAF mut pts had shorter long-term survival.