FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109).

Abstract

PURPOSE:

This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer.

PATIENTS AND METHODS:

The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was ≥ 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival.

RESULTS:

A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12).

CONCLUSION:

The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.

• Authors: Dominik P Modest, Uwe M Martens, Jorge Riera-Knorrenschild, Jobst Greeve, Axel Florschütz, Swen Wessendorf, Thomas Ettrich, Stephan Kanzler, Dominik Nörenberg, Jens Ricke, Max Seidensticker, Swantje Held, Petra Buechner-Steudel, Jens Atzpodien, Volker Heinemann, Thomas Seufferlein, Andrea Tannapfel, Anke C Reinacher-Schick, Michael Geissler
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 37 Issue 35 Pg. 3401-3411 (12 10 2019) ISSN: 1527-7755 [Electronic] United States
• PMID: 31609637 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Oxaliplatin
• Bevacizumab
• Panitumumab
• Irinotecan
• ras Proteins
• Leucovorin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab (administration & dosage)
• Case-Control Studies
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Female
• Follow-Up Studies
• Humans
• Irinotecan (administration & dosage)
• Leucovorin (administration & dosage)
• Liver Neoplasms (drug therapy, genetics, secondary)
• Male
• Middle Aged
• Mutation
• Oxaliplatin (administration & dosage)
• Panitumumab (administration & dosage)
• Prognosis
• Survival Rate
• ras Proteins (genetics)