Upfront Modified FOLFOXIRI Plus Panitumumab for <i>RAS/BRAF</i> Wild-Type Metastatic Colorectal Cancer: Final Results of the Phase III TRIPLETE Study

V Veronica Conca (Veronica Conca, MD, PhD, Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy; Daniele Rossini, MD, PhD, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; and Chiara Cremolini, MD, PhD, Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy) D Daniele Rossini C Carlotta Antoniotti S Sara Lonardi F Filippo Pietrantonio R Roberto Moretto (Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy) L Lorenzo Antonuzzo (Azienda Ospedaliero Universitaria Careggi, Florence, Italy) G Giovanni Randon D Daniele Lavacchi C Carmelo Pozzo (Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy) F Federica Marmorino F Francesca Bergamo E Emiliano Tamburini (Oncology Department and Palliative Care, Cardinale Panico Tricase City Hospital, Tricase, Italy) A Alessandro Passardi (Medical Oncology, IRST-IRCCS "Dino Amadori", Meldola, Italy) R Roberta Fazio (Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, NA, Italy) S Sabina Murgioni (Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy) B Beatrice Borelli (Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy) A Angela Buonadonna (Department of Medical Oncology San Vito site, CRO Aviano-IRCCS, Aviano, Italy) M Marco Maria Germani (Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy) V Vincenzo Formica (Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, Italy) M Martina Carullo (Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana and Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy) R Roberto Bordonaro G Giuseppe Aprile A Alberto Zaniboni (Medical Oncology Unit, Poliambulanza Foundation, Brescia, Italy) G Gianluca Masi L Luca Boni (Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Azienda Ospedaliera Metropolitana, Genova, Italy) C Chiara Cremolini

Abstract

We report 5-year results of the phase III randomized TRIPLETE study. Eligible patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) received first-line modified fluorouracil, leucovorin, oxaliplatin (mFOLFOX)/panitumumab (control group, n = 217) versus modified fluorouracil, leucovorin, oxaliplatin, irinotecan (mFOLFOXIRI)/panitumumab (experimental group, n = 218). We present overall survival (OS) and updated outcomes in the intention-to-treat population. The median follow-up was 60.2 months (IQR, 49.3-70.0). The median OS was 41.1 and 33.3 months for experimental and control groups, respectively (hazard ratio [HR], 0.79 [95% CI, 0.63 to 0.99]; P = .049). OS outcomes favored the experimental group regardless of clinical features. No differences in objective response rate (primary end point; 75%/78%, odds ratio, 0.84 [95% CI, 0.54 to 1.31]; P = .442), early tumor shrinkage rate ( P = .954), depth of response ( P = .573), no residual tumor resection rate ( P = .329), and progression-free survival (HR, 0.95 [95% CI, 0.78 to 1.16]; P = .606) were confirmed. Among patients alive at the time of disease progression, the median postprogression survival was 24.6 and 17.7 months for experimental and control groups, respectively (HR, 0.79 [95% CI, 0.62 to 1.01]; P = .062). Similar proportions of patients in both groups received subsequent lines of therapy (control/experimental: second line 73%/71%, third line 51%/49%, fourth line 31%/32%), as well as nonpalliative locoregional treatments (control/experimental: 16%/16%). Upfront mFOLFOXIRI/panitumumab significantly improves OS compared with mFOLFOX/panitumumab in patients with RAS/BRAF wild-type mCRC.

Article Details

Volume / Issue Vol. 44, Issue 5
Published February 10, 2026
Pages 361-369
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (27)

V

Veronica Conca

Veronica Conca, MD, PhD, Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy; Daniele Rossini, MD, PhD, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; and Chiara Cremolini, MD, PhD, Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy

D

Daniele Rossini

C

Carlotta Antoniotti

S

Sara Lonardi

F

Filippo Pietrantonio

R

Roberto Moretto

Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

L

Lorenzo Antonuzzo

Azienda Ospedaliero Universitaria Careggi, Florence, Italy

G

Giovanni Randon

D

Daniele Lavacchi

C

Carmelo Pozzo

Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy

F

Federica Marmorino

F

Francesca Bergamo

E

Emiliano Tamburini

Oncology Department and Palliative Care, Cardinale Panico Tricase City Hospital, Tricase, Italy

A

Alessandro Passardi

Medical Oncology, IRST-IRCCS "Dino Amadori", Meldola, Italy

R

Roberta Fazio

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, NA, Italy

S

Sabina Murgioni

Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy

B

Beatrice Borelli

Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

A

Angela Buonadonna

Department of Medical Oncology San Vito site, CRO Aviano-IRCCS, Aviano, Italy

M

Marco Maria Germani

Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

V

Vincenzo Formica

Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, Italy

M

Martina Carullo

Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana and Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

R

Roberto Bordonaro

G

Giuseppe Aprile

A

Alberto Zaniboni

Medical Oncology Unit, Poliambulanza Foundation, Brescia, Italy

G

Gianluca Masi

L

Luca Boni

Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Azienda Ospedaliera Metropolitana, Genova, Italy

C

Chiara Cremolini