Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in context
Summary: Background: The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated RAS wild-type metastatic colorectal cancer (mCRC) patients. Methods: In this final phase 2 trial analysis, adult mCRC patients responding to six cycl...
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Elsevier
2025-01-01
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| author | Arndt Stahler Meinolf Karthaus Stefan Fruehauf Ullrich Graeven Lothar Müller Ludwig Fischer von Weikersthal Karel Caca Eray Goekkurt Alexej Ballhausen Greta Sommerhäuser Annabel H.S. Alig Swantje Held Armin Jarosch David Horst Anke Reinacher-Schick Stefan Kasper Volker Heinemann Sebastian Stintzing Tanja Trarbach Dominik P. Modest |
| author_facet | Arndt Stahler Meinolf Karthaus Stefan Fruehauf Ullrich Graeven Lothar Müller Ludwig Fischer von Weikersthal Karel Caca Eray Goekkurt Alexej Ballhausen Greta Sommerhäuser Annabel H.S. Alig Swantje Held Armin Jarosch David Horst Anke Reinacher-Schick Stefan Kasper Volker Heinemann Sebastian Stintzing Tanja Trarbach Dominik P. Modest |
| author_sort | Arndt Stahler |
| collection | DOAJ |
| description | Summary: Background: The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated RAS wild-type metastatic colorectal cancer (mCRC) patients. Methods: In this final phase 2 trial analysis, adult mCRC patients responding to six cycles of FU/FA, oxaliplatin and panitumumab were randomized (1:1, open-label) to maintenance of either FU/FA + panitumumab or FU/FA alone. The primary endpoint was superiority of progression-free survival of maintenance (PFS; time from random assignment to progression/death) in favour of FU/FA + panitumumab. Secondary endpoints included PFS of re-induction (PFS re-ind.), time to failure of strategy (TFS) and overall survival (OS). The trial is registered with ClinicalTrials.gov (NCT01991873). Findings: In 248 patients of the Full Analysis Set recruited between May 2014 and February 2021, with a median observation of 64.0 (range 12.5–86.3) months and 59.7 (range 3.7–97.3) months in the treatment arms, 230 events for PFS (92.7%) and 196 events for OS (79.0%) were recorded. Adding panitumumab to FU/FA resulted in significantly longer PFS (8.8 versus 5.8 months, HR = 0.73 (95% CI 0.56–0.94), P = 0.015), shorter PFS re-ind. (4.1 versus 7.4 months, HR = 1.93 (95% CI 1.33–2.82), P < 0.001), comparable TFS (17.1 versus 15.7 months, HR = 0.98 (95% CI 0.68–1.42), P = 0.92) and numerically longer OS (29.9 versus 24.7 months, HR = 0.85 (95% CI 0.64–1.12), P = 0.24). The most frequent adverse event (AE) grade ≥3 was rash (FU/FA + panitumumab: n = 15, 12.0%, FU/FA: n = 17, 6.9%). 141 patients (37.3%) experienced at least one serious AE One treatment-related death occurred (neutropenic sepsis, FU/FA). Interpretation: Panitumumab plus FU/FA might be considered a standard of care maintenance regimen since a potential re-induction therapy with panitumumab cannot be guaranteed at the time of maintenance treatment decision. Funding: Amgen. |
| format | Article |
| id | doaj-art-3328135f1bac488383d509a19fc7642e |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-01-01 |
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| series | EClinicalMedicine |
| spelling | doaj-art-3328135f1bac488383d509a19fc7642e2025-01-22T05:43:30ZengElsevierEClinicalMedicine2589-53702025-01-0179103004Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in contextArndt Stahler0Meinolf Karthaus1Stefan Fruehauf2Ullrich Graeven3Lothar Müller4Ludwig Fischer von Weikersthal5Karel Caca6Eray Goekkurt7Alexej Ballhausen8Greta Sommerhäuser9Annabel H.S. Alig10Swantje Held11Armin Jarosch12David Horst13Anke Reinacher-Schick14Stefan Kasper15Volker Heinemann16Sebastian Stintzing17Tanja Trarbach18Dominik P. Modest19Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, Germany; Corresponding author. Division of Hematology, Oncology and Cancer Immunology (CCM), Medical Department, Charité Universitaetsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.Department of Hematology and Oncology, Munich Hospital Neuperlach, Munich, GermanyDr Hancken Hospital, Stade, GermanyKliniken Maria Hilf GmbH, Mönchengladbach, GermanyOncology Practice UnterEms, Leer, GermanyGesundheitszentrum St Marien, Amberg, GermanyDepartment of Gastroenterology, Hematology and Oncology, Hospital Ludwigsburg, Ludwigsburg, GermanyPractice of Hematology and Oncology (HOPE), Hamburg, Germany; University Cancer Center Hamburg (UCCH), Hamburg, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, GermanyClinAssess GmbH, Leverkusen, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pathology, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pathology, Berlin, Germany; German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, GermanySt Joseph Hospital, Bochum, GermanyGerman Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany; Department of Medical Oncology, West German Cancer Center, Westdeutsches Tumorzentrum, University Hospital of Essen, Essen, GermanyGerman Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany; Department of Medicine 2I and Comprehensive Cancer Center, University Hospital (LMU), Munich, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, Germany; German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, GermanyDepartment of Medical Oncology, West German Cancer Center, Westdeutsches Tumorzentrum, University Hospital of Essen, Essen, Germany; Reha-Zentrum am Meer, Bad Zwischenahn, Niedersachsen, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, Germany; German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, GermanySummary: Background: The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated RAS wild-type metastatic colorectal cancer (mCRC) patients. Methods: In this final phase 2 trial analysis, adult mCRC patients responding to six cycles of FU/FA, oxaliplatin and panitumumab were randomized (1:1, open-label) to maintenance of either FU/FA + panitumumab or FU/FA alone. The primary endpoint was superiority of progression-free survival of maintenance (PFS; time from random assignment to progression/death) in favour of FU/FA + panitumumab. Secondary endpoints included PFS of re-induction (PFS re-ind.), time to failure of strategy (TFS) and overall survival (OS). The trial is registered with ClinicalTrials.gov (NCT01991873). Findings: In 248 patients of the Full Analysis Set recruited between May 2014 and February 2021, with a median observation of 64.0 (range 12.5–86.3) months and 59.7 (range 3.7–97.3) months in the treatment arms, 230 events for PFS (92.7%) and 196 events for OS (79.0%) were recorded. Adding panitumumab to FU/FA resulted in significantly longer PFS (8.8 versus 5.8 months, HR = 0.73 (95% CI 0.56–0.94), P = 0.015), shorter PFS re-ind. (4.1 versus 7.4 months, HR = 1.93 (95% CI 1.33–2.82), P < 0.001), comparable TFS (17.1 versus 15.7 months, HR = 0.98 (95% CI 0.68–1.42), P = 0.92) and numerically longer OS (29.9 versus 24.7 months, HR = 0.85 (95% CI 0.64–1.12), P = 0.24). The most frequent adverse event (AE) grade ≥3 was rash (FU/FA + panitumumab: n = 15, 12.0%, FU/FA: n = 17, 6.9%). 141 patients (37.3%) experienced at least one serious AE One treatment-related death occurred (neutropenic sepsis, FU/FA). Interpretation: Panitumumab plus FU/FA might be considered a standard of care maintenance regimen since a potential re-induction therapy with panitumumab cannot be guaranteed at the time of maintenance treatment decision. Funding: Amgen.http://www.sciencedirect.com/science/article/pii/S2589537024005832Metastatic colorectal cancerPanitumumabMaintenanceRAS wild-typeRe-induction |
| spellingShingle | Arndt Stahler Meinolf Karthaus Stefan Fruehauf Ullrich Graeven Lothar Müller Ludwig Fischer von Weikersthal Karel Caca Eray Goekkurt Alexej Ballhausen Greta Sommerhäuser Annabel H.S. Alig Swantje Held Armin Jarosch David Horst Anke Reinacher-Schick Stefan Kasper Volker Heinemann Sebastian Stintzing Tanja Trarbach Dominik P. Modest Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in context EClinicalMedicine Metastatic colorectal cancer Panitumumab Maintenance RAS wild-type Re-induction |
| title | Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in context |
| title_full | Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in context |
| title_fullStr | Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in context |
| title_full_unstemmed | Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in context |
| title_short | Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trialResearch in context |
| title_sort | panitumumab plus 5 fluorouracil and folinic acid or 5 fluorouracil and folinic acid alone as maintenance therapy in ras wild type metastatic colorectal cancer panama aio krk 0212 final efficacy analysis of a randomised open label phase 2 trialresearch in context |
| topic | Metastatic colorectal cancer Panitumumab Maintenance RAS wild-type Re-induction |
| url | http://www.sciencedirect.com/science/article/pii/S2589537024005832 |
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