Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)

Sampsa Kinos; Helga Hagman; Päivi Halonen; Leena-Maija Soveri; Mary O'Reilly; Per Pfeiffer; Jan-Erik Frödin; Halfdan Sorbye; Eetu Heervä; Gabor Liposits; Raija Kallio; Annika Ålgars; Raija Ristamäki; Tapio Salminen; Maarit Bärlund; Carl-Henrik  Shah; Ray McDermott; Rebecka Röckert; Petra Flygare; Johannes Kwakman; Arco Teske; Cornelis Punt; Bengt Glimelius; Pia Österlund

doi:10.2340/1651-226X.2024.24023

Authors

Sampsa Kinos Department of Oncology, Tays Cancer Center, Tampere University Hospital, Tampere, Finland; Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland https://orcid.org/0000-0001-8060-0193
Helga Hagman Department of Oncology, Skåne University Hospital, Malmö, Sweden https://orcid.org/0000-0002-4427-1123
Päivi Halonen Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland https://orcid.org/0000-0002-9760-0840
Leena-Maija Soveri Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland https://orcid.org/0000-0001-5210-2891
Mary O'Reilly Department of Oncology, St Vincent’s University Hospital and University College Dublin, Dublin, Ireland https://orcid.org/0000-0001-7987-4154
Per Pfeiffer Department of Oncology, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0002-2925-0586
Jan-Erik Frödin Department of Oncology, Karolinska University Hospital, Stockholm, Sweden https://orcid.org/0000-0003-1985-2046
Halfdan Sorbye Department of Oncology, Haukeland University Hospital, Bergen, Norway https://orcid.org/0000-0002-7132-6214
Eetu Heervä Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland https://orcid.org/0000-0002-6134-1170
Gabor Liposits Department of Oncology, Regional Hospital West Jutland, Hjørring, Denmark https://orcid.org/0000-0002-8204-3949
Raija Kallio Department of Oncology, Oulu University and University Hospital, Oulu, Finland https://orcid.org/0000-0002-5912-496X
Annika Ålgars Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland https://orcid.org/0000-0002-9841-1881
Raija Ristamäki Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland https://orcid.org/0000-0001-6817-3045
Tapio Salminen Department of Oncology, Tays Cancer Center, Tampere University Hospital, Tampere, Finland; Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland https://orcid.org/0000-0003-4116-2260
Maarit Bärlund Department of Oncology, Tays Cancer Center, Tampere University Hospital, Tampere, Finland; Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland https://orcid.org/0000-0002-1469-5654
Carl-Henrik Shah Department of Oncology, Karolinska University Hospital, Stockholm, Sweden https://orcid.org/0000-0002-1412-5985
Ray McDermott Department of Oncology, St Vincent’s University Hospital and University College Dublin, Dublin, Ireland https://orcid.org/0000-0002-8952-4315
Rebecka Röckert Department of Oncology, Uppsala University, Uppsala, Sweden https://orcid.org/0000-0002-6306-3733
Petra Flygare Department of Oncology, Sundsvall Hospital, Sundsvall, Sweden https://orcid.org/0000-0002-8817-1239
Johannes Kwakman Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands https://orcid.org/0000-0002-8187-7124
Arco Teske Department of Cardiology, University Medical Centre, Utrecht University, Utrecht, The Netherlands https://orcid.org/0000-0001-5305-1619
Cornelis Punt Depatment of Epidemiology, Jules Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherland https://orcid.org/0000-0003-0846-1445
Bengt Glimelius Department of Oncology, Uppsala University, Uppsala, Sweden https://orcid.org/0000-0002-5440-791X
Pia Österlund Department of Oncology, Tays Cancer Center, Tampere University Hospital, Tampere, Finland; Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland; Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; rTema Cancer, Department of GI-cancer, Karolinska University Hospital, Stockholm, Sweden https://orcid.org/0000-0002-7124-3515

DOI:

https://doi.org/10.2340/1651-226X.2024.24023

Keywords:

metastatic colorectal cancer, fluoropyrimidines, S-1, cardiotoxicity, capecitabine, 5-fluorouracil, metastasectomy

Abstract

Background and purpose: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study.

Materials and methods: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients.

Results: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs.

Interpretation: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.

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Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)

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