F Marmorino1, D Rossini1, S Lonardi2, R Moretto1, G Zucchelli1, G Aprile3, E Dell'Aquila4, M Ratti5, F Bergamo2, G Masi1, F Urbano6, M Ronzoni7, M Libertini8, B Borelli1, G Randon9, A Buonadonna10, G Allegrini11, N Pella12, V Ricci13, A Boccaccino1, T P Latiano14, S Cordio15, A Passardi16, E Tamburini17, L Boni18, A Falcone1, C Cremolini19. 1. Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa. 2. Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Veneto Institute of Oncology - IRCCS, Padova. 3. Department of Oncology, General and University Hospital, Udine; Department of Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza. 4. Department of Medical Oncology, Campus Biomedico University, Roma. 5. Oncology Department, Oncology Unit, ASST of Cremona, Cremona. 6. Department of Radiological Science, Oncology and Pathology, Policlinico Umberto I, "Sapienza" University of Rome, Roma. 7. Department of Oncology, Istituto Scientifico San Raffaele IRCSS, Milano. 8. Medical Oncology Unit, Poliambulanza Foundation, Brescia. 9. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. 10. Department of Medical Oncology, IRCCS CRO National Cancer Institute, Aviano. 11. Department of Medical Oncology, Unit of Medical Oncology, Livorno Hospital, Azienda Toscana Nord Ovest, Livorno. 12. Department of Oncology, General and University Hospital, Udine. 13. Department of Oncology, S. Croce and Carle Teaching Hospital, Cuneo. 14. Oncology Unit, Foundation IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo. 15. Medical Oncology Unit, ARNAS Garibaldi Catania, Catania. 16. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola. 17. Department of Medical Oncology, Card. G. Panico Hospital of Tricase, Tricase. 18. Clinical Trials Coordinating Center, Toscano Cancer Institute, University Hospital Careggi, Firenze, Italy. 19. Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa. Electronic address: chiaracremolini@gmail.com.
Abstract
BACKGROUND: The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. PATIENTS AND METHODS: Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates. RESULTS: Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%). CONCLUSIONS: The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.
BACKGROUND: The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancerpatients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. PATIENTS AND METHODS: Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates. RESULTS: Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%). CONCLUSIONS: The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.
Authors: Annika Kurreck; Volker Heinemann; Ludwig Fischer von Weikersthal; Thomas Decker; Florian Kaiser; Jens Uhlig; Michael Schenk; Jens Freiberg-Richter; Bettina Peuser; Claudio Denzlinger; Ullrich Graeven; Kathrin Heinrich; Swantje Held; Arndt Stahler; Annabel Helga Sophie Alig; Ivan Jelas; Jobst C von Einem; Sebastian Stintzing; Clemens Giessen-Jung; Dominik P Modest Journal: Front Oncol Date: 2022-02-18 Impact factor: 6.244