Consensus Molecular Subtypes as Biomarkers of Fluorouracil and Folinic Acid Maintenance Therapy With or Without Panitumumab in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa, AIO KRK 0212)

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Consensus Molecular Subtypes as Biomarkers of Fluorouracil and Folinic Acid Maintenance Therapy With or Without Panitumumab in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa, AIO KRK 0212). / Stahler, Arndt; Hoppe, Beeke; Na, Il-Kang; Keilholz, Luisa; Müller, Lothar; Karthaus, Meinolf; Fruehauf, Stefan; Graeven, Ullrich; Fischer von Weikersthal, Ludwig; Goekkurt, Eray; Kasper, Stefan; Kind, Andreas Jay; Kurreck, Annika; Alig, Annabel Helga Sophie; Held, Swantje; Reinacher-Schick, Anke; Heinemann, Volker; Horst, David; Jarosch, Armin; Stintzing, Sebastian; Trarbach, Tanja; Modest, Dominik Paul.

in: J CLIN ONCOL, Jahrgang 41, Nr. 16, 01.06.2023, S. 2975-2987.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Stahler, A, Hoppe, B, Na, I-K, Keilholz, L, Müller, L, Karthaus, M, Fruehauf, S, Graeven, U, Fischer von Weikersthal, L, Goekkurt, E, Kasper, S, Kind, AJ, Kurreck, A, Alig, AHS, Held, S, Reinacher-Schick, A, Heinemann, V, Horst, D, Jarosch, A, Stintzing, S, Trarbach, T & Modest, DP 2023, 'Consensus Molecular Subtypes as Biomarkers of Fluorouracil and Folinic Acid Maintenance Therapy With or Without Panitumumab in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa, AIO KRK 0212)', J CLIN ONCOL, Jg. 41, Nr. 16, S. 2975-2987. https://doi.org/10.1200/JCO.22.02582

APA

Stahler, A., Hoppe, B., Na, I-K., Keilholz, L., Müller, L., Karthaus, M., Fruehauf, S., Graeven, U., Fischer von Weikersthal, L., Goekkurt, E., Kasper, S., Kind, A. J., Kurreck, A., Alig, A. H. S., Held, S., Reinacher-Schick, A., Heinemann, V., Horst, D., Jarosch, A., ... Modest, D. P. (2023). Consensus Molecular Subtypes as Biomarkers of Fluorouracil and Folinic Acid Maintenance Therapy With or Without Panitumumab in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa, AIO KRK 0212). J CLIN ONCOL, 41(16), 2975-2987. https://doi.org/10.1200/JCO.22.02582

Vancouver

Bibtex

@article{2bb1dc03eb7e4356b58c3555f519afe2,
title = "Consensus Molecular Subtypes as Biomarkers of Fluorouracil and Folinic Acid Maintenance Therapy With or Without Panitumumab in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa, AIO KRK 0212)",
abstract = "PURPOSE: Consensus molecular subtypes (CMSs) were evaluated as prognostic and predictive biomarkers of patients with RAS wild-type metastatic colorectal cancer (mCRC) receiving fluorouracil and folinic acid (FU/FA) with or without panitumumab (Pmab) after Pmab + mFOLFOX6 induction within the randomized phase II PanaMa trial.METHODS: CMSs were determined in the safety set (ie, patients that received induction) and full analysis set (FAS; ie, randomly assigned patients who received maintenance) and correlated with median progression-free survival (PFS) and overall survival (OS) since the start of induction or maintenance treatment and objective response rates (ORRs). Hazard ratios (HRs) and 95% CI were calculated by univariate/multivariate Cox regression analyses.RESULTS: Of 377 patients of the safety set, 296 (78.5%) had available CMS data: CMS1/2/3/4: 29 (9.8%)/122 (41.2%)/33 (11.2%)/112 (37.8%) and unclassifiable: 17 (5.7%). The CMSs were prognostic biomarkers in terms of PFS (P < .0001), OS (P < .0001), and ORR (P = .02) since the start of induction treatment. In FAS patients (n = 196), with CMS2/4 tumors, the addition of Pmab to FU/FA maintenance therapy was associated with longer PFS (CMS2: HR, 0.58 [95% CI, 0.36 to 0.95], P = .03; CMS4: HR, 0.63 [95% CI, 0.38 to 1.03], P = .07) and OS (CMS2: HR, 0.88 [95% CI, 0.52 to 1.52], P = .66; CMS4: HR, 0.54 [95% CI, 0.30 to 0.96], P = .04). The CMS interacted significantly with treatment in terms of PFS (CMS2 v CMS1/3: P = .02; CMS4 v CMS1/3: P = .03) and OS (CMS2 v CMS1/3: P = .03; CMS4 v CMS1/3: P < .001).CONCLUSION: The CMS had a prognostic impact on PFS, OS, and ORR in RAS wild-type mCRC. In PanaMa, Pmab + FU/FA maintenance was associated with beneficial outcomes in CMS2/4, whereas no benefit was observed in CMS1/3 tumors.",
keywords = "Humans, Panitumumab/therapeutic use, Colorectal Neoplasms/drug therapy, Leucovorin/therapeutic use, Fluorouracil/therapeutic use, Colonic Neoplasms/drug therapy, Rectal Neoplasms/drug therapy, Biomarkers, Antineoplastic Combined Chemotherapy Protocols/adverse effects",
author = "Arndt Stahler and Beeke Hoppe and Il-Kang Na and Luisa Keilholz and Lothar M{\"u}ller and Meinolf Karthaus and Stefan Fruehauf and Ullrich Graeven and {Fischer von Weikersthal}, Ludwig and Eray Goekkurt and Stefan Kasper and Kind, {Andreas Jay} and Annika Kurreck and Alig, {Annabel Helga Sophie} and Swantje Held and Anke Reinacher-Schick and Volker Heinemann and David Horst and Armin Jarosch and Sebastian Stintzing and Tanja Trarbach and Modest, {Dominik Paul}",
year = "2023",
month = jun,
day = "1",
doi = "10.1200/JCO.22.02582",
language = "English",
volume = "41",
pages = "2975--2987",
journal = "J CLIN ONCOL",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "16",

}

RIS

TY - JOUR

T1 - Consensus Molecular Subtypes as Biomarkers of Fluorouracil and Folinic Acid Maintenance Therapy With or Without Panitumumab in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa, AIO KRK 0212)

AU - Stahler, Arndt

AU - Hoppe, Beeke

AU - Na, Il-Kang

AU - Keilholz, Luisa

AU - Müller, Lothar

AU - Karthaus, Meinolf

AU - Fruehauf, Stefan

AU - Graeven, Ullrich

AU - Fischer von Weikersthal, Ludwig

AU - Goekkurt, Eray

AU - Kasper, Stefan

AU - Kind, Andreas Jay

AU - Kurreck, Annika

AU - Alig, Annabel Helga Sophie

AU - Held, Swantje

AU - Reinacher-Schick, Anke

AU - Heinemann, Volker

AU - Horst, David

AU - Jarosch, Armin

AU - Stintzing, Sebastian

AU - Trarbach, Tanja

AU - Modest, Dominik Paul

PY - 2023/6/1

Y1 - 2023/6/1

N2 - PURPOSE: Consensus molecular subtypes (CMSs) were evaluated as prognostic and predictive biomarkers of patients with RAS wild-type metastatic colorectal cancer (mCRC) receiving fluorouracil and folinic acid (FU/FA) with or without panitumumab (Pmab) after Pmab + mFOLFOX6 induction within the randomized phase II PanaMa trial.METHODS: CMSs were determined in the safety set (ie, patients that received induction) and full analysis set (FAS; ie, randomly assigned patients who received maintenance) and correlated with median progression-free survival (PFS) and overall survival (OS) since the start of induction or maintenance treatment and objective response rates (ORRs). Hazard ratios (HRs) and 95% CI were calculated by univariate/multivariate Cox regression analyses.RESULTS: Of 377 patients of the safety set, 296 (78.5%) had available CMS data: CMS1/2/3/4: 29 (9.8%)/122 (41.2%)/33 (11.2%)/112 (37.8%) and unclassifiable: 17 (5.7%). The CMSs were prognostic biomarkers in terms of PFS (P < .0001), OS (P < .0001), and ORR (P = .02) since the start of induction treatment. In FAS patients (n = 196), with CMS2/4 tumors, the addition of Pmab to FU/FA maintenance therapy was associated with longer PFS (CMS2: HR, 0.58 [95% CI, 0.36 to 0.95], P = .03; CMS4: HR, 0.63 [95% CI, 0.38 to 1.03], P = .07) and OS (CMS2: HR, 0.88 [95% CI, 0.52 to 1.52], P = .66; CMS4: HR, 0.54 [95% CI, 0.30 to 0.96], P = .04). The CMS interacted significantly with treatment in terms of PFS (CMS2 v CMS1/3: P = .02; CMS4 v CMS1/3: P = .03) and OS (CMS2 v CMS1/3: P = .03; CMS4 v CMS1/3: P < .001).CONCLUSION: The CMS had a prognostic impact on PFS, OS, and ORR in RAS wild-type mCRC. In PanaMa, Pmab + FU/FA maintenance was associated with beneficial outcomes in CMS2/4, whereas no benefit was observed in CMS1/3 tumors.

AB - PURPOSE: Consensus molecular subtypes (CMSs) were evaluated as prognostic and predictive biomarkers of patients with RAS wild-type metastatic colorectal cancer (mCRC) receiving fluorouracil and folinic acid (FU/FA) with or without panitumumab (Pmab) after Pmab + mFOLFOX6 induction within the randomized phase II PanaMa trial.METHODS: CMSs were determined in the safety set (ie, patients that received induction) and full analysis set (FAS; ie, randomly assigned patients who received maintenance) and correlated with median progression-free survival (PFS) and overall survival (OS) since the start of induction or maintenance treatment and objective response rates (ORRs). Hazard ratios (HRs) and 95% CI were calculated by univariate/multivariate Cox regression analyses.RESULTS: Of 377 patients of the safety set, 296 (78.5%) had available CMS data: CMS1/2/3/4: 29 (9.8%)/122 (41.2%)/33 (11.2%)/112 (37.8%) and unclassifiable: 17 (5.7%). The CMSs were prognostic biomarkers in terms of PFS (P < .0001), OS (P < .0001), and ORR (P = .02) since the start of induction treatment. In FAS patients (n = 196), with CMS2/4 tumors, the addition of Pmab to FU/FA maintenance therapy was associated with longer PFS (CMS2: HR, 0.58 [95% CI, 0.36 to 0.95], P = .03; CMS4: HR, 0.63 [95% CI, 0.38 to 1.03], P = .07) and OS (CMS2: HR, 0.88 [95% CI, 0.52 to 1.52], P = .66; CMS4: HR, 0.54 [95% CI, 0.30 to 0.96], P = .04). The CMS interacted significantly with treatment in terms of PFS (CMS2 v CMS1/3: P = .02; CMS4 v CMS1/3: P = .03) and OS (CMS2 v CMS1/3: P = .03; CMS4 v CMS1/3: P < .001).CONCLUSION: The CMS had a prognostic impact on PFS, OS, and ORR in RAS wild-type mCRC. In PanaMa, Pmab + FU/FA maintenance was associated with beneficial outcomes in CMS2/4, whereas no benefit was observed in CMS1/3 tumors.

KW - Humans

KW - Panitumumab/therapeutic use

KW - Colorectal Neoplasms/drug therapy

KW - Leucovorin/therapeutic use

KW - Fluorouracil/therapeutic use

KW - Colonic Neoplasms/drug therapy

KW - Rectal Neoplasms/drug therapy

KW - Biomarkers

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

U2 - 10.1200/JCO.22.02582

DO - 10.1200/JCO.22.02582

M3 - SCORING: Journal article

C2 - 37018649

VL - 41

SP - 2975

EP - 2987

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 16

ER -