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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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)
Creators Name:	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., Stintzing, S., Trarbach, T. and Modest, D.P.
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:	Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Colonic Neoplasms, Colorectal Neoplasms, Fluorouracil, Leucovorin, Panitumumab, Rectal Neoplasms
Source:	Journal of Clinical Oncology
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Volume:	41
Number:	16
Page Range:	2975-2987
Date:	1 June 2023
Official Publication:	https://doi.org/10.1200/jco.22.02582
PubMed:	View item in PubMed

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