Filippo Pietrantonio1, Fausto Petrelli2, Andrea Coinu3, Maria Di Bartolomeo4, Karen Borgonovo5, Claudia Maggi6, Mary Cabiddu7, Roberto Iacovelli8, Ilaria Bossi9, Veronica Lonati10, Mara Ghilardi11, Filippo de Braud12, Sandro Barni13. 1. Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Electronic address: filippo.pietrantonio@istitutotumori.mi.it. 2. Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: faupe@libero.it. 3. Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: artefice2003@hotmail.com. 4. Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Electronic address: maria.dibartolomeo@istitutotumori.mi.it. 5. Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: karenbf_it@yahoo.it. 6. Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Electronic address: claudia.maggi@istitutotumori.mi.it. 7. Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: mary_cabiddu@yahoo.it. 8. Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Electronic address: roberto.iacovelli@istitutotumori.mi.it. 9. Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Electronic address: ilaria.bossi@istitutotumori.mi.it. 10. Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: lo.ve@tiscali.it. 11. Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: mara.ghily@alice.it. 12. Department of Medical Oncology, Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Electronic address: filippo.debraud@istitutotumori.mi.it. 13. Department of Oncology, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Piazzale Ospedale 1, 24047 Treviglio (BG), Italy. Electronic address: sandro.barni@ospedale.treviglio.bg.it.
Abstract
BACKGROUND: Wild type RAS (RAS-wt) status is predictive of the activities of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab (C) and panitumumab (P). We examined the impact of C and P on progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in advanced colorectal cancer (CRC) patients who have RAS-wt/BRAF-mutant (BRAF-mut) status. METHODS: Randomised trials that compared C or P plus chemotherapy (or C or P monotherapy) with standard therapy or best supportive care (BSC) were included. We used published hazard ratios (HRs) if they were available, or we derived treatment estimates from other survival data. Pooled estimates of the treatment efficacy of anti-EGFR-based therapy with C or P for the RAS-wt/BRAF-mut subgroup were calculated with the random-effect inverse variance weighted method. All statistical tests were two-sided. RESULTS: Nine phase III trials and one phase II trial (six first-line and two second-line trials, plus two trials involving chemorefractory patients), that included 463 RAS-wt/BRAF-mut CRC patients, were analysed. Overall, the addition of C or P treatment in the BRAF-mut subgroup did not significantly improve PFS (HR, 0.88; 95% confidence interval (CI), 0.67-1.14; p=0.33), OS (HR, 0.91; 95% CI, 0.62-1.34; p=0.63) and ORR (relative risk, 1.31; 95% CI 0.83-2.08, p=0.25) compared with control regimens. CONCLUSIONS: C- or P-based therapy did not increase the benefit of standard therapy or the BSC in RAS-wt/BRAF-mut CRC patients. These findings support BRAF mutation assessment before initiation of treatment with anti-EGFR monoclonal antibodies.
BACKGROUND: Wild type RAS (RAS-wt) status is predictive of the activities of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab (C) and panitumumab (P). We examined the impact of C and P on progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in advanced colorectal cancer (CRC) patients who have RAS-wt/BRAF-mutant (BRAF-mut) status. METHODS: Randomised trials that compared C or P plus chemotherapy (or C or P monotherapy) with standard therapy or best supportive care (BSC) were included. We used published hazard ratios (HRs) if they were available, or we derived treatment estimates from other survival data. Pooled estimates of the treatment efficacy of anti-EGFR-based therapy with C or P for the RAS-wt/BRAF-mut subgroup were calculated with the random-effect inverse variance weighted method. All statistical tests were two-sided. RESULTS: Nine phase III trials and one phase II trial (six first-line and two second-line trials, plus two trials involving chemorefractory patients), that included 463 RAS-wt/BRAF-mut CRC patients, were analysed. Overall, the addition of C or P treatment in the BRAF-mut subgroup did not significantly improve PFS (HR, 0.88; 95% confidence interval (CI), 0.67-1.14; p=0.33), OS (HR, 0.91; 95% CI, 0.62-1.34; p=0.63) and ORR (relative risk, 1.31; 95% CI 0.83-2.08, p=0.25) compared with control regimens. CONCLUSIONS: C- or P-based therapy did not increase the benefit of standard therapy or the BSC in RAS-wt/BRAF-mut CRC patients. These findings support BRAF mutation assessment before initiation of treatment with anti-EGFR monoclonal antibodies.
Authors: Antonia R Sepulveda; Stanley R Hamilton; Carmen J Allegra; Wayne Grody; Allison M Cushman-Vokoun; William K Funkhouser; Scott E Kopetz; Christopher Lieu; Noralane M Lindor; Bruce D Minsky; Federico A Monzon; Daniel J Sargent; Veena M Singh; Joseph Willis; Jennifer Clark; Carol Colasacco; R Bryan Rumble; Robyn Temple-Smolkin; Christina B Ventura; Jan A Nowak Journal: J Mol Diagn Date: 2017-02-06 Impact factor: 5.568
Authors: Benny Johnson; Zhaohui Jin; Mark J Truty; Rory L Smoot; David M Nagorney; Michael L Kendrick; Benjamin R Kipp; Axel Grothey Journal: Oncologist Date: 2017-09-13