Roberto Moretto1, Andrew Elliott2, Daniele Rossini1,3, Rossana Intini4, Veronica Conca1,3, Filippo Pietrantonio5, Andrea Sartore-Bianchi6, Carlotta Antoniotti1,3, Cosimo Rasola4,7, Mario Scartozzi8, Massimiliano Salati9,10, Nicoletta Pella11, Maria Alessandra Calegari12, Martina Carullo1,3, Francesca Corti5, Gianluca Mauri6, Matteo Fassan13,14, Gianluca Masi1,3, Pavel Brodskiy2, Heinz-Josef Lenz15, Anthony Shields16, Sara Lonardi17, Michael Korn2, Chiara Cremolini1,3. 1. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 2. Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA. 3. Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy. 4. Oncology Unit 1, Veneto Institute of Oncology-IRCCS, Padua, Italy. 5. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 6. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. 7. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. 8. Medical Oncology, University and University Hospital of Cagliari, Cagliari, Italy. 9. Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy. 10. PhD Program Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy. 11. Department of Oncology, ASUFC University Hospital of Udine, Udine, Italy. 12. Comprensive Cancer Center, UOC di Oncologia Medica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy. 13. Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy. 14. Veneto Institute of Oncology-IRCCS, Padua, Italy. 15. Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. 16. Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. 17. Oncology Unit 3, Veneto Institute of Oncology-IRCCS, Padua, Italy. sara.lonardi@iov.veneto.it.
Abstract
BACKGROUND: Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0. METHODS: The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples. RESULTS: A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population. CONCLUSIONS: Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.
BACKGROUND: Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0. METHODS: The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples. RESULTS: A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population. CONCLUSIONS: Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.
Authors: Van Morris; Michael J Overman; Zhi-Qin Jiang; Christopher Garrett; Shweta Agarwal; Cathy Eng; Bryan Kee; David Fogelman; Arvind Dasari; Robert Wolff; Dipen Maru; Scott Kopetz Journal: Clin Colorectal Cancer Date: 2014-06-23 Impact factor: 4.481
Authors: Ben Tran; Scott Kopetz; Jeanne Tie; Peter Gibbs; Zhi-Qin Jiang; Christopher H Lieu; Atin Agarwal; Dipen M Maru; Oliver Sieber; Jayesh Desai Journal: Cancer Date: 2011-03-31 Impact factor: 6.860
Authors: Susan D Richman; Matthew T Seymour; Philip Chambers; Faye Elliott; Catherine L Daly; Angela M Meade; Graham Taylor; Jennifer H Barrett; Philip Quirke Journal: J Clin Oncol Date: 2009-11-02 Impact factor: 44.544
Authors: E Van Cutsem; A Cervantes; R Adam; A Sobrero; J H Van Krieken; D Aderka; E Aranda Aguilar; A Bardelli; A Benson; G Bodoky; F Ciardiello; A D'Hoore; E Diaz-Rubio; J-Y Douillard; M Ducreux; A Falcone; A Grothey; T Gruenberger; K Haustermans; V Heinemann; P Hoff; C-H Köhne; R Labianca; P Laurent-Puig; B Ma; T Maughan; K Muro; N Normanno; P Österlund; W J G Oyen; D Papamichael; G Pentheroudakis; P Pfeiffer; T J Price; C Punt; J Ricke; A Roth; R Salazar; W Scheithauer; H J Schmoll; J Tabernero; J Taïeb; S Tejpar; H Wasan; T Yoshino; A Zaanan; D Arnold Journal: Ann Oncol Date: 2016-07-05 Impact factor: 32.976
Authors: Helen Davies; Graham R Bignell; Charles Cox; Philip Stephens; Sarah Edkins; Sheila Clegg; Jon Teague; Hayley Woffendin; Mathew J Garnett; William Bottomley; Neil Davis; Ed Dicks; Rebecca Ewing; Yvonne Floyd; Kristian Gray; Sarah Hall; Rachel Hawes; Jaime Hughes; Vivian Kosmidou; Andrew Menzies; Catherine Mould; Adrian Parker; Claire Stevens; Stephen Watt; Steven Hooper; Rebecca Wilson; Hiran Jayatilake; Barry A Gusterson; Colin Cooper; Janet Shipley; Darren Hargrave; Katherine Pritchard-Jones; Norman Maitland; Georgia Chenevix-Trench; Gregory J Riggins; Darell D Bigner; Giuseppe Palmieri; Antonio Cossu; Adrienne Flanagan; Andrew Nicholson; Judy W C Ho; Suet Y Leung; Siu T Yuen; Barbara L Weber; Hilliard F Seigler; Timothy L Darrow; Hugh Paterson; Richard Marais; Christopher J Marshall; Richard Wooster; Michael R Stratton; P Andrew Futreal Journal: Nature Date: 2002-06-09 Impact factor: 49.962
Authors: J F Seligmann; D Fisher; C G Smith; S D Richman; F Elliott; S Brown; R Adams; T Maughan; P Quirke; J Cheadle; M Seymour; G Middleton Journal: Ann Oncol Date: 2017-03-01 Impact factor: 32.976