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)

Item Type:	Article
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. and Hoppe, B. and Na, I.K. and Keilholz, L. and Müller, L. and Karthaus, M. and Fruehauf, S. and Graeven, U. and Fischer von Weikersthal, L. and Goekkurt, E. and Kasper, S. and Kind, A.J. and Kurreck, A. and Alig, A.H.S. and Held, S. and Reinacher-Schick, A. and Heinemann, V. and Horst, D. and Jarosch, A. and Stintzing, S. and 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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