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.
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The PanaMa trial showed an OS benefit from the addition of panitunimab to 5-FU and FA maintenance in CMS4 patients.
“Recently, results from the PanaMa trial showed an OS benefit from the addition of panitunimab to 5-FU and FA maintenance in CMS4 patients (61).”
From Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine (2024) · cites this paper as [61]
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- Authors
- 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., & Modest, D. P.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- German Cancer Research Center (DE)
- Oncology Practice UnterEms, Leer, Germany
- München Klinik Neuperlach (DE)
- Klinik Dr. Hancken (DE)
- Kliniken Maria Hilf (DE)
- Klinikum St Marien, Oncology, Amberg, Germany
- University Cancer Center Hamburg (DE)
- ClinAssess (Germany) (DE)
- Department of Hematology, Oncology and Palliative Care, St Josef-Hospital, Ruhr-University, Bochum, Germany
- Essen University Hospital (DE)
- ORCID
- Stahler, Arndt
- Hoppe, Beeke
- Na, Il-Kang
- Keilholz, Luisa
- Müller, Lothar
- Karthaus, Meinolf
- Fruehauf, Stefan
- Graeven, Ullrich
- 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
- Venue
- Journal of Clinical Oncology
- Published
- 2023-06-01
- Volume
- 41
- Issue
- 16
- Pages
- 2975-2987
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W4362634073
- Cited by
- 16
- References
- 32
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 5 · 2023: 1
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- consensus molecular subtypes, metastatic colorectal cancer, RAS wild-type, panitumumab, predictive biomarkers, prognostic factors, progression-free survival, overall survival, objective response rate, CMS4, treatment response prediction, molecular subtypes
- MeSH terms
- Panitumumab, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Colonic Neoplasms, Fluorouracil, Humans, Rectal Neoplasms, Colorectal Neoplasms, Biomarkers
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