mFOLFOXIRI/Panitumumab vs mFOLFOX/Panitumumab for the Initial Treatment of RAS and BRAF Wild-Type Metastatic Colorectal Cancer

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In an Italian phase III trial (TRIPLETE) presented at the 2022 ASCO Annual Meeting (Abstract LBA3505) and simultaneously published in the Journal of Clinical Oncology, Rossini et al found that mFOLFOXIRI (modified fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus panitumumab did not improve objective response rate vs mFOLFOX (modified fluorouracil, leucovorin, and oxaliplatin) plus panitumumab in the initial treatment of RAS and BRAF wild-type metastatic colorectal cancer.

Study Details

In the multicenter open-label trial, 435 patients were randomly assigned between September 2017 and September 2021 to receive mFOLFOXIRI/panitumumab (n = 218) or mFOLFOX/panitumumab (n = 217) for up to 12 cycles, followed by fluorouracil/leucovorin plus panitumumab until disease progression. The primary endpoint was objective response rate on Response Evaluation Criteria in Solid Tumors version 1.1.


Objective response was observed in 160 patients (73%) in the mFOLFOXIRI/panitumumab group vs 165 patients (76%) patients in the mFOLFOX/panitumumab group (odds ratio = 0.87, 95% confidence interval [CI] = 0.56–1.34, P = .526), with complete response in 7% vs 7%. No significant differences were observed in the disease control rate (91% vs 93%, P = .496), early tumor shrinkage rate (57% vs 58%, P = .878), or R0 resection rate among the 33 vs 30 patients undergoing surgery.


  • mFOLFOXIRI/panitumumab did not improve objective response rate vs mFOLFOX/panitumumab.
  • No difference in progression-free survival was observed.

After a median follow-up of 26.5 moths (interquartile range = 13.7–35.9 months), median progression-free survival was 12.7 months (95% CI = 11.1–15.5 months) in the mFOLFOXIRI/panitumumab group vs 12.3 months (95% CI = 11.1–14.3 months) in the mFOLFOX/panitumumab group (hazard ratio = 0.88, 95% CI = 0.70–1.11, P = .277).

Adverse Events

The most common grade 3 or 4 adverse events in the mFOLFOXIRI/panitumumab group were neutropenia (32% vs 20% in the mFOLFOX/panitumumab group), diarrhea (23% vs 7%), acneiform rash (19% vs 29%), stomatitis (7% vs 7%), hypokalemia (7% vs 4%), and fatigue (7% vs 2%). Among gastrointestinal adverse events of any grade, nausea occurred in 52% vs 35% of patients, vomiting in 24% vs 13%, and diarrhea in 72% vs 40%. Three treatment-related deaths occurred in the mFOLFOXIRI/panitumumab group, due to diarrhea in two patients and sepsis in one.

The investigators concluded, “The intensification of the upfront chemotherapy backbone in combination with panitumumab does not provide additional benefit in terms of treatment activity at the price of increased gastrointestinal toxicity in patients with RAS and BRAF wild-type metastatic colorectal cancer.”

Chiara Cremolini, MD, PhD, of the Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the GONO (Gruppo Oncologico del Nord Ovest) Foundation and by Amgen. For full disclosures of the study authors, visit

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