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, Vol. 41, No. 16, 01.06.2023, p. 2975-2987.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -
