Dataset Information

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.

ABSTRACT:

Purpose

To verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC).

Methods

TRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable RAS and BRAF wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.1. Hypothesizing an ORR of 60% in the control group, 432 cases provided 90% power to a two-sided chi-square test for heterogeneity with a two-sided alpha error of .05 to detect ≥ 15% differences between arms (ClinicalTrials.gov identifier: NCT03231722).

Results

From September 2017 to September 2021, 435 patients were enrolled (control group/experimental group: 217/218) in 57 Italian sites. One hundred sixty (73%) patients treated with mFOLFOXIRI plus panitumumab and 165 (76%) patients treated with modified FOLFOX plus panitumumab achieved RECIST response (odds ratio 0.87, 95% CI, 0.56 to 1.34, P = .526). No differences in early tumor shrinkage rate (57%/58%, P = .878) and deepness of response (median: 48%/47%, P = .845) were reported, nor in R0 resection rate (25%/29%, P = .317). No significant difference between arms was reported in terms of progression-free survival (median progression-free survival: 12.7 in the experimental group v 12.3 months in the control group, hazard ratio: 0.88, 95% CI, 0.70 to 1.11, P = .277).

Conclusion

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 wt mCRC.

SUBMITTER: Rossini D

PROVIDER: S-EPMC9426812 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With <i>RAS/BRAF</i> Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO.

Rossini Daniele D Antoniotti Carlotta C Lonardi Sara S Pietrantonio Filippo F Moretto Roberto R Antonuzzo Lorenzo L Boccaccino Alessandra A Morano Federica F Brugia Marco M Pozzo Carmelo C Marmorino Federica F Bergamo Francesca F Tamburini Emiliano E Passardi Alessandro A Randon Giovanni G Murgioni Sabina S Borelli Beatrice B Buonadonna Angela A Giordano Mirella M Fontanini Gabriella G Conca Veronica V Formica Vincenzo V Aglietta Massimo M Bordonaro Roberto R Aprile Giuseppe G Masi Gianluca G Boni Luca L Cremolini Chiara C

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20220606 25

<h4>Purpose</h4>To verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for <i>RAS</i> and <i>BRAF</i> wild-type (wt) metastatic colorectal cancer (mCRC).<h4>Methods</h4>TRIPLETE was a prospective, open-label, phase III trial in which prev ...[more]

PMID: 35666229

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