Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series
ABSTRACT Background In patients receiving anti‐cancer treatment, cachexia results in poorer oncological outcomes. However, there is limited understanding and no systematic review of oncological endpoints in cancer cachexia (CC) trials. This review examines oncological endpoints in CC clinical trials...
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2025-04-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
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| Online Access: | https://doi.org/10.1002/jcsm.13756 |
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| author | Olav Dajani Iain Philips Ester Kristine Størkson Trude R. Balstad Leo R. Brown Asta Bye Ross Dolan Christine Greil Marianne Hjermstad Gunnhild Jakobsen Stein Kaasa James McDonald Inger Ottestad Judith Sayers Melanie Simpson Mariana S. Sousa Ola Magne Vagnildhaug Michael S. Yule Barry J. A. Laird Richard J. E. Skipworth Tora S. Solheim Mark Stares Jann Arends the Cancer Cachexia Endpoints Working Group |
| author_facet | Olav Dajani Iain Philips Ester Kristine Størkson Trude R. Balstad Leo R. Brown Asta Bye Ross Dolan Christine Greil Marianne Hjermstad Gunnhild Jakobsen Stein Kaasa James McDonald Inger Ottestad Judith Sayers Melanie Simpson Mariana S. Sousa Ola Magne Vagnildhaug Michael S. Yule Barry J. A. Laird Richard J. E. Skipworth Tora S. Solheim Mark Stares Jann Arends the Cancer Cachexia Endpoints Working Group |
| author_sort | Olav Dajani |
| collection | DOAJ |
| description | ABSTRACT Background In patients receiving anti‐cancer treatment, cachexia results in poorer oncological outcomes. However, there is limited understanding and no systematic review of oncological endpoints in cancer cachexia (CC) trials. This review examines oncological endpoints in CC clinical trials. Methods An electronic literature search of MEDLINE, Embase and Cochrane databases (1990–2023) was performed. Eligibility criteria comprised participants ≥ 18 years old; controlled design; ≥ 40 participants; and a cachexia intervention for > 14 days. Trials reporting at least one oncological endpoint were selected for analysis. Data extraction was performed using Covidence and followed PRISMA guidelines and the review was registered (PROSPERO CRD42022276710). Results Fifty‐seven trials were eligible, totalling 9743 patients (median: 107, IQR: 173). Twenty‐six (46%) trials focussed on a single tumour site: eight in lung, six in pancreatic, six in head and neck and six in GI cancers. Forty‐two (74%) studies included patients with Stage III/IV disease, and 41 (70%) included patients receiving palliative anti‐cancer treatment. Ten studies (18%) involved patients on curative treatment. Twenty‐eight (49%) studies used pharmacological interventions, 29 (50%) used oral nutrition, and two (4%) used enteral or parenteral nutrition. Reported oncological endpoints included overall survival (OS, n = 46 trials), progression‐free survival (PFS, n = 7), duration of response (DR, n = 1), response rate (RR, n = 9), completion of treatment (TC, n = 11) and toxicity/adverse events (AE, n = 42). Median OS differed widely from 60 to 3468 days. Of the 46 studies, only three reported a significant positive effect on survival. Seven trials showed a difference in AE, four in TC, one in PFS and one in RR. Reported significances were unreliable due to missing adjustments for extensive multiple testing. Only three of the six trials using OS as the primary endpoint reported pre‐trial sample size calculations, but only one recruited the planned number of patients. Conclusion In CC trials, oncological endpoints were mostly secondary and only few significant findings have been reported. Due to heterogeneity in oncological settings, nutritional and metabolic status and interventions, firm conclusions about CC treatment are not possible. OS and AE are relevant endpoints, but future trials targeting clinically meaningful hazard ratios will required more homogeneous patient cohorts, adequate pre‐trial power analyses and adherence to statistical testing standards. |
| format | Article |
| id | doaj-art-7798ca82cf8844e58199fe1ae1b24e0e |
| institution | OA Journals |
| issn | 2190-5991 2190-6009 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
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| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj-art-7798ca82cf8844e58199fe1ae1b24e0e2025-08-20T02:09:09ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-04-01162n/an/a10.1002/jcsm.13756Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints SeriesOlav Dajani0Iain Philips1Ester Kristine Størkson2Trude R. Balstad3Leo R. Brown4Asta Bye5Ross Dolan6Christine Greil7Marianne Hjermstad8Gunnhild Jakobsen9Stein Kaasa10James McDonald11Inger Ottestad12Judith Sayers13Melanie Simpson14Mariana S. Sousa15Ola Magne Vagnildhaug16Michael S. Yule17Barry J. A. Laird18Richard J. E. Skipworth19Tora S. Solheim20Mark Stares21Jann Arends22the Cancer Cachexia Endpoints Working GroupRegional Advisory Unit for Palliative Care, Dept. of Oncology, Oslo University Hospital/European Palliative Care Research Centre (PRC), Dept. of Oncology, Oslo University Hospital, and Institute of Clinical Medicine University of Oslo Oslo NorwayEdinburgh Cancer Research Centre, Institute of Genetics and Cancer University of Edinburgh Edinburgh UKRegional Advisory Unit for Palliative Care, Dept. of Oncology, Oslo University Hospital/European Palliative Care Research Centre (PRC), Dept. of Oncology, Oslo University Hospital, and Institute of Clinical Medicine University of Oslo Oslo NorwayDepartment of Clinical Medicine, Clinical Nutrition Research Group UiT The Arctic University of Norway Tromsø NorwayRoyal Infirmary of Edinburgh Clinical Surgery University of Edinburgh Edinburgh UKDepartment of Nursing and Health Promotion, Faculty of Health Sciences Oslo Metropolitan University Oslo NorwayAcademic Unit of Surgery University of Glasgow, Glasgow Royal Infirmary Glasgow UKDepartment of Medicine I, Medical Center ‐ University of Freiburg, Faculty of Medicine University of Freiburg Freiburg GermanyRegional Advisory Unit for Palliative Care, Dept. of Oncology, Oslo University Hospital/European Palliative Care Research Centre (PRC), Dept. of Oncology, Oslo University Hospital, and Institute of Clinical Medicine University of Oslo Oslo NorwayDepartment of Public Health and Nursing Norwegian University of Science and Technology Trondheim NorwayRegional Advisory Unit for Palliative Care, Dept. of Oncology, Oslo University Hospital/European Palliative Care Research Centre (PRC), Dept. of Oncology, Oslo University Hospital, and Institute of Clinical Medicine University of Oslo Oslo NorwayEdinburgh Cancer Research Centre, Institute of Genetics and Cancer University of Edinburgh Edinburgh UKDepartment of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine University of Oslo Oslo NorwayEdinburgh Cancer Research Centre, Institute of Genetics and Cancer University of Edinburgh Edinburgh UKDepartment of Public Health and Nursing Norwegian University of Science and Technology Trondheim NorwayImproving Palliative, Aged and Chronic Care Through Clinical Research and Translation (IMPACCT) University of Technology Sydney Sydney AustraliaDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences NTNU ‐ Norwegian University of Science and Technology Trondheim NorwayEdinburgh Cancer Research Centre, Institute of Genetics and Cancer University of Edinburgh Edinburgh UKEdinburgh Cancer Research Centre, Institute of Genetics and Cancer University of Edinburgh Edinburgh UKRoyal Infirmary of Edinburgh Clinical Surgery University of Edinburgh Edinburgh UKDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences NTNU ‐ Norwegian University of Science and Technology Trondheim NorwayEdinburgh Cancer Research Centre, Institute of Genetics and Cancer University of Edinburgh Edinburgh UKDepartment of Medicine I, Medical Center ‐ University of Freiburg, Faculty of Medicine University of Freiburg Freiburg GermanyABSTRACT Background In patients receiving anti‐cancer treatment, cachexia results in poorer oncological outcomes. However, there is limited understanding and no systematic review of oncological endpoints in cancer cachexia (CC) trials. This review examines oncological endpoints in CC clinical trials. Methods An electronic literature search of MEDLINE, Embase and Cochrane databases (1990–2023) was performed. Eligibility criteria comprised participants ≥ 18 years old; controlled design; ≥ 40 participants; and a cachexia intervention for > 14 days. Trials reporting at least one oncological endpoint were selected for analysis. Data extraction was performed using Covidence and followed PRISMA guidelines and the review was registered (PROSPERO CRD42022276710). Results Fifty‐seven trials were eligible, totalling 9743 patients (median: 107, IQR: 173). Twenty‐six (46%) trials focussed on a single tumour site: eight in lung, six in pancreatic, six in head and neck and six in GI cancers. Forty‐two (74%) studies included patients with Stage III/IV disease, and 41 (70%) included patients receiving palliative anti‐cancer treatment. Ten studies (18%) involved patients on curative treatment. Twenty‐eight (49%) studies used pharmacological interventions, 29 (50%) used oral nutrition, and two (4%) used enteral or parenteral nutrition. Reported oncological endpoints included overall survival (OS, n = 46 trials), progression‐free survival (PFS, n = 7), duration of response (DR, n = 1), response rate (RR, n = 9), completion of treatment (TC, n = 11) and toxicity/adverse events (AE, n = 42). Median OS differed widely from 60 to 3468 days. Of the 46 studies, only three reported a significant positive effect on survival. Seven trials showed a difference in AE, four in TC, one in PFS and one in RR. Reported significances were unreliable due to missing adjustments for extensive multiple testing. Only three of the six trials using OS as the primary endpoint reported pre‐trial sample size calculations, but only one recruited the planned number of patients. Conclusion In CC trials, oncological endpoints were mostly secondary and only few significant findings have been reported. Due to heterogeneity in oncological settings, nutritional and metabolic status and interventions, firm conclusions about CC treatment are not possible. OS and AE are relevant endpoints, but future trials targeting clinically meaningful hazard ratios will required more homogeneous patient cohorts, adequate pre‐trial power analyses and adherence to statistical testing standards.https://doi.org/10.1002/jcsm.13756adverse eventscachexiacancerclinical trialssurvival |
| spellingShingle | Olav Dajani Iain Philips Ester Kristine Størkson Trude R. Balstad Leo R. Brown Asta Bye Ross Dolan Christine Greil Marianne Hjermstad Gunnhild Jakobsen Stein Kaasa James McDonald Inger Ottestad Judith Sayers Melanie Simpson Mariana S. Sousa Ola Magne Vagnildhaug Michael S. Yule Barry J. A. Laird Richard J. E. Skipworth Tora S. Solheim Mark Stares Jann Arends the Cancer Cachexia Endpoints Working Group Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series Journal of Cachexia, Sarcopenia and Muscle adverse events cachexia cancer clinical trials survival |
| title | Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series |
| title_full | Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series |
| title_fullStr | Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series |
| title_full_unstemmed | Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series |
| title_short | Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series |
| title_sort | oncological and survival endpoints in cancer cachexia clinical trials systematic review 6 of the cachexia endpoints series |
| topic | adverse events cachexia cancer clinical trials survival |
| url | https://doi.org/10.1002/jcsm.13756 |
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