Benefit from upfront FOLFOXIRI and bevacizumab in BRAFV600E-mutated metastatic colorectal cancer patients: does primary tumour location matter?

Antineoplastic Combined Chemotherapy Protocols / therapeutic use Bevacizumab / therapeutic use Camptothecin / analogs & derivatives Colonic Neoplasms / drug therapy Colorectal Neoplasms / drug therapy Fluorouracil / adverse effects Humans Leucovorin / adverse effects Organoplatinum Compounds Rectal Neoplasms / chemically induced

Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
09 2022
Historique:
received: 04 01 2022
accepted: 09 05 2022
revised: 02 04 2022
pubmed: 7 6 2022
medline: 3 9 2022
entrez: 6 6 2022
Statut: ppublish

Résumé

Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0. The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples. A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population. Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.

Sections du résumé

BACKGROUND
Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0.
METHODS
The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples.
RESULTS
A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population.
CONCLUSIONS
Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.

Identifiants

DOI: 10.1038/s41416-022-01852-0 PMID: 35665778 PMC: PMC9428147
pubmed: 35665778
doi: 10.1038/s41416-022-01852-0
pii: 10.1038/s41416-022-01852-0
pmc: PMC9428147
doi:

Substances chimiques

Organoplatinum Compounds 0
Bevacizumab 2S9ZZM9Q9V
Leucovorin Q573I9DVLP
Fluorouracil U3P01618RT
Camptothecin XT3Z54Z28A

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

957-967

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Roberto Moretto (R)

Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
ORCID: 0000-0001-8456-9269

Andrew Elliott (A)

Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.

Daniele Rossini (D)

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.

Rossana Intini (R)

Oncology Unit 1, Veneto Institute of Oncology-IRCCS, Padua, Italy.

Veronica Conca (V)

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.
ORCID: 0000-0001-7713-4005

Filippo Pietrantonio (F)

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
ORCID: 0000-0002-8530-8420

Andrea Sartore-Bianchi (A)

Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
ORCID: 0000-0003-0780-0409

Carlotta Antoniotti (C)

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.

Cosimo Rasola (C)

Oncology Unit 1, Veneto Institute of Oncology-IRCCS, Padua, Italy.
Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Mario Scartozzi (M)

Medical Oncology, University and University Hospital of Cagliari, Cagliari, Italy.

Massimiliano Salati (M)

Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy.
PhD Program Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy.

Nicoletta Pella (N)

Department of Oncology, ASUFC University Hospital of Udine, Udine, Italy.

Maria Alessandra Calegari (MA)

Comprensive Cancer Center, UOC di Oncologia Medica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Martina Carullo (M)

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.

Francesca Corti (F)

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

Gianluca Mauri (G)

Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

Matteo Fassan (M)

Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy.
Veneto Institute of Oncology-IRCCS, Padua, Italy.
ORCID: 0000-0001-6515-5482

Gianluca Masi (G)

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.

Pavel Brodskiy (P)

Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.

Heinz-Josef Lenz (HJ)

Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
ORCID: 0000-0003-2178-9568

Anthony Shields (A)

Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.

Sara Lonardi (S)

Oncology Unit 3, Veneto Institute of Oncology-IRCCS, Padua, Italy. sara.lonardi@iov.veneto.it.
ORCID: 0000-0002-7593-8138

Michael Korn (M)

Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ, USA.

Chiara Cremolini (C)

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.
ORCID: 0000-0002-0520-4841

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Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
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Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
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Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Protocoles de polychimiothérapie antinéoplasique › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Bévacizumab › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Composés hétérocycliques › Alcaloïdes › Camptothécine › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Tumeurs de l'intestin › Tumeurs du côlon › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du rectum › Tumeurs colorectales › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Pyrimidinones › Uracile › Fluorouracil › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Enzymes et coenzymes › Coenzymes › Tétrahydrofolates › Formyltétrahydrofolates › Leucovorine › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Composés chimiques organiques › Composés organométalliques › Composés organiques du platine › Benefit from upfront FOLFOXIRI and bevacizumab...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du rectum › Tumeurs colorectales › Tumeurs du rectum › Benefit from upfront FOLFOXIRI and bevacizumab...