First Line mFOLFOXIRI + PANITUMUMAB vs mFOLFOX + PANITUMUMAB IN RAS AND BRAF WT METASTATIC COLORECTAL CANCER PATIENTS

Summary

* The association of FOLFOX (5-fluoruracil, folinic acid, and oxaliplatin) and pan is a standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC patients. * The phase III TRIBE trial recently demonstrated that FOLFOXIRI (5-fluoruracil, folinic acid, oxaliplatin and irinotecan) plus bev significantly prolongs PFS and OS and increases RECIST response rate, ETS and DoR, as compared to FOLFIRI (5-fluoruracil folinic acid, and irinotecan) plus bev. The advantage provided by the intensification of the upfront chemotherapy backbone is independent of RAS and BRAF mutational status. * Some phase II trials recently assessed the safety and activity of the combination of three-drugs chemotherapy regimens with an anti-EGFR monoclonal antibody. Promising activity results in terms of RECIST response rate and R0 resection rate have been achieved, with some safety concerns with special regards to gastrointestinal toxicity. * In the phase II randomized MACBETH study the combination of a modified schedule of FOLFOXIRI with cetuximab determined remarkable activity results, with an acceptable and manageable safety profile. * The optimal duration of the upfront treatment with chemotherapy plus anti-EGFRs is not established. The phase II MACRO-2 trial suggested that interrupting FOLFOX after 4 months while continuing cet alone as maintenance, is a reasonable option. * Activity parameters (RECIST response rate, ETS, DoR) are clinically relevant endpoints, associated with longer survival, in particular with anti-EGFR moAb-based treatment. On the basis of these considerations, we designed the present phase III randomized trial of first-line mFOLFOXIRI plus pan versus mFOLFOX6 plus pan in RAS and BRAF wt unresectable mCRC patients.

Timeline

Start

2017-09-13

Primary completion

2022-06-15

Completion

2022-06-24

Publications

• Conca V, Rossini D, Antoniotti C, Lonardi S, Pietrantonio F, Moretto R, Antonuzzo L, Randon G, Lavacchi D, Pozzo C, Marmorino F, Bergamo F, Tamburini E, Passardi A, Fazio R, Murgioni S, Borelli B, Buonadonna A, Germani MM, Formica V, Carullo M, Bordonaro R, Aprile G, Zaniboni A, Masi G, Boni L, Cremolini C. Upfront Modified FOLFOXIRI Plus Panitumumab for RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Final Results of the Phase III TRIPLETE Study. J Clin Oncol. 2026 Feb 10;44(5):361-369. doi: 10.1200/JCO-25-01337. Epub 2026 Jan 8.
• Sposito C, Pietrantonio F, Maspero M, Di Benedetto F, Vivarelli M, Tisone G, De Carlis L, Romagnoli R, Gruttadauria S, Colledan M, Agnes S, Ettorre G, Baccarani U, Torzilli G, Di Sandro S, Pinelli D, Caccamo L, Sartore Bianchi A, Spreafico C, Torri V, Mazzaferro V. Improving Outcome of Selected Patients With Non-Resectable Hepatic Metastases From Colorectal Cancer With Liver Transplantation: A Prospective Parallel Trial (COLT trial). Clin Colorectal Cancer. 2023 Jun;22(2):250-255. doi: 10.1016/j.clcc.2023.01.003. Epub 2023 Feb 3.
• Rossini D, Antoniotti C, Lonardi S, Pietrantonio F, Moretto R, Antonuzzo L, Boccaccino A, Morano F, Brugia M, Pozzo C, Marmorino F, Bergamo F, Tamburini E, Passardi A, Randon G, Murgioni S, Borelli B, Buonadonna A, Giordano M, Fontanini G, Conca V, Formica V, Aglietta M, Bordonaro R, Aprile G, Masi G, Boni L, Cremolini C. Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO. J Clin Oncol. 2022 Sep 1;40(25):2878-2888. doi: 10.1200/JCO.22.00839. Epub 2022 Jun 6.
• Borelli B, Moretto R, Lonardi S, Bonetti A, Antoniotti C, Pietrantonio F, Masi G, Burgio V, Marmorino F, Salvatore L, Rossini D, Zaniboni A, Zucchelli G, Martignetti A, Di Battista M, Pella N, Passardi A, Boccaccino A, Leone F, Colombo C, Granetto C, Vannini F, Marsico VA, Martinelli E, Antonuzzo L, Vitello S, Delliponti L, Boni L, Cremolini C, Falcone A. TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer. ESMO Open. 2018 Jul 9;3(4):e000403. doi: 10.1136/esmoopen-2018-000403. eCollection 2018.

Drugs

Indications