Meeting
2022 ASCO Annual Meeting
Consensus molecular subtypes (CMS) as prognostic and predictive biomarkers of panitumumab (Pmab), fluorouracil and folinic acid (FU/FA) or FU/FA maintenance therapy following Pmab-FOLFOX induction in RAS wildtype metastatic colorectal cancer (mCRC): PANAMA trial (AIO-KRK-0212).
Authors
Beeke Hoppe
Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany
Beeke Hoppe , Dominik Paul Modest , Luisa Keilholz , Il-Kang Na , Meinolf Karthaus , Stefan Fruehauf , Ullrich Graeven , Ludwig Fischer Von Weikersthal , Eray Goekkurt , Anke C. Reinacher-Schick , Stefan Kasper , Andreas Jay Kind , Annika Kurreck , Swantje Held , Volker Heinemann , David Horst , Armin Jarosch , Sebastian Stintzing , Tanja Trarbach , Arndt Stahler
Organizations
Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany, Charité- Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Department of Hematology, Oncology, and Cancer Immunology (CVK), Berlin, Germany, Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, Germany, Klinikum Neuperlach/ Klinikum Harlaching, Department of Hematology, Oncology, and Palliative Care, Munich, Germany, Dr Hancken Hospital, Stade, Germany, Kliniken Maria Hilf GmbH, Department of Hematology, Oncology, and Gastroenterology, Moenchengladbach, Germany, Gesundheitszentrum St. Marien, Amberg, Germany, Practice of Hematology and Oncology (HOPE), Hamburg, Germany, Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany, ClinAssess GmbH, Leverkusen, Germany, University Hospital, LMU Munich, Department of Medicine III, and Comprehensive Cancer Center Munich, Munich, Germany, Charité Medizinische Universitaet Berlin, Institute for Pathology, Berlin, Germany, Charité– Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology, and Cancer Immunology (CCM), Berlin, Germany, Reha-Zentrum am Meer, Bad Zwischenahn, Germany, Charité- Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Department of Hematology, Oncology, and Cancer Immunology (CCM), Berlin, Germany
Research Funding
Other Foundation
Pharmaceutical/Biotech Company
Background: Consensus molecular subtypes (CMS1-4) of colorectal cancer were evaluated as prognostic and predictive biomarkers in the PANAMA trial. PANAMA compared maintenance therapy with panitumumab (Pmab) and fluorouracil/folinic acid (FU/FA) vs. FU/FA alone after Pmab-FOLFOX induction therapy in RAS wildtype mCRC. Methods: Gene expression was measured after mRNA isolation in 179 of 248 patients of the full analysis set. The analysis was conducted using a customized Nanostring PanCancer Progression Panel. The original CMS classifier was re-derived for Nanostring data using a multinomial regression analysis.Median progression-free (PFS) and overall survival (OS) since start of maintenance were estimated by Kaplan-Meier-method and Cox-regression, using the log rank test. Objective response rates (ORR) of maintenance therapy were compared by Chi-square-test. Results: Prevalence of CMS was: CMS1, n = 15 (8.4 %); CMS2, n = 82 (45.8 %); CMS3, n = 20 (11.2 %) and CMS4, n = 62 (34.6 %). A prognostic impact of CMS regardless of treatment was not evident for PFS (p = 0.245) and OS (p = 0.169), but for ORR (p = 0.022), with CMS1 and CMS3 being associated with unfavourable efficacy during maintenance therapy. Potential predictive effects of CMS were observed in patients with CMS2 and CMS4 tumours. In CMS2 and CMS4 tumours, ORR was significantly higher when treated with Pmab-FU/FA in maintenance therapy (CMS2: 56.5% vs 30.6%, p = 0.026; CMS4: 55.6% vs. 28.6%, p = 0.040). In patients with CMS2 mCRC, this translated into a significant effect on PFS (Hazard ratio: 0.61 (95% CI 0.38 – 0.99) p = 0.046 (Table). Conclusions: CMS have limited prognostic impact for pmab-based maintenance therapy. However, CMS2 and CMS4 are positively associated with Pmab efficacy during maintenance therapy in the PANAMA trial. Further trials are necessary to confirm these results.
| CMS1 n = 15 | CMS2 n = 82 | CMS3 n = 20 | CMS4 n = 62 | |||||
|---|---|---|---|---|---|---|---|---|
| Pmab-FU/FA n = 8 | FU/FA n = 7 | Pmab-FU/FA n = 46 | FU/FA n = 36 | Pmab-FU/FA n = 8 | FU/FA n = 12 | Pmab-FU/FA n = 27 | FU/FA n = 35 | |
| PFS (months) | 5.3 | 4.1 | 9.2 | 6.0 | 5.8 | 5.6 | 8.8 | 6.0 |
| HR (95%CI) p (log-rank) | 0.86 (0.29 – 2.51) p = 0.783 | 0.61 (0.38 – 0.99) p = 0.046 | 0.84 (0.33 – 2.13) p = 0.708 | 0.77 (0.45 – 1.32) p = 0.343 | ||||
| OS (months) | 10.6 | 15.4 | 28.7 | 26.7 | 22.2 | 26.0 | 42.7 | 23.9 |
| HR (95%CI) p (log-rank) | 0.77 (0.22 – 2.77) p = 0.693 | 0.93 (0.50 – 1.74) p = 0.823 | 0.83 (0.23 – 2.96) p = 0.772 | 0.62 (0.31 – 1.25) p = 0.181 | ||||
| ORR, % | 0.0 | 14.3 | 56.5 | 30.6 | 0.0 | 41.6 | 55.6 | 28.6 |
| p (Chi-square) | p = 0.467 | p = 0.026 | p = 0.109 | p = 0.040 | ||||
Legend: CMS = consensus molecular subtypes; Pmab = panitumumab; FU/FA = fluorouracil/folinic acid; PFS = progression-free survival; OS = overall survival; HR = hazard ratio; CI = confidence interval; ORR = objective response rate.
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Abstract Details
Session Type
Poster Session
Session Title
Gastrointestinal Cancer—Colorectal and Anal
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Epidemiology/Outcomes
Citation
J Clin Oncol 40, 2022 (suppl 16; abstr 3537)
DOI
10.1200/JCO.2022.40.16_suppl.3537
Abstract #
3537
Poster Bd #
331
Abstract Disclosures
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