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Treatment breaks in first line treatment of advanced colorectal cancer: an individual patient data meta-analysis

Adams, Richard, Goey, Kaitlyn, Chibaudel, Benoist, Koopman, Miriam, Punt, Cornelis, Arnold, Dirk, Hinke, Axel, Hegewisch-Becker, Susanna, de Gramont, Aimery, Labianca, Roberto, Diaz Rubio, Eduardo, Magne Tveit, Kjell, Wasan, Harpreet, Kaplan, Richard, Brown, Louise, Maughan, Tim and Fisher, David 2021. Treatment breaks in first line treatment of advanced colorectal cancer: an individual patient data meta-analysis. Cancer Treatment Reviews 99 , 102226. 10.1016/j.ctrv.2021.102226

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Abstract

Background Intermittent systemic anti-cancer therapy in patients with advanced colorectal cancer (aCRC) may improve quality of life without compromising overall survival (OS). We aimed to use individual patient data meta-analysis (IPDMA) from multiple randomised controlled trials evaluating intermittent strategies to inform clinical practice. We also aimed to validate whether thrombocytosis as a predictive biomarker identified patients with significantly reduced OS receiving a complete treatment break. Patients and Methods An IPDMA of intermittent strategy impact on survival was undertaken, including all relevant trials in which data were available. Intermittent strategies were classified into two groups: a planned stopping of all therapy (“treatment break strategy”; 6 trials; 2,907 patients) or to the same treatment omitting oxaliplatin (“maintenance strategy”; 3 trials; 1,271 patients). The primary analysis sample was of patients successfully completing induction therapy. Additionally, a pre-planned analysis of the predictive value of thrombocytosis on survival under a continuous versus an intermittent strategy was undertaken. Results All trials had comparable inclusion criteria. The overall IPDMA of intermittent therapy versus continuous therapy demonstrated no detriment in OS (HR=1.03 [95% CI 0.93-1.14]), whether from complete break (HR 1.04 [95% CI 0.87-1.26]) or maintenance strategies (HR 0.99 [95% CI 0.87-1.13]). Thrombocytosis was confirmed as a marker of poor prognosis in aCRC, but did not predict for OS detriment from treatment break strategies (interaction HR=0.97 [95% CI 0.66-1.40] compared to continuous therapy). Conclusion The highest levels of evidence from this IPMDA indicate no detriment in survival for patients receiving an intermittent therapy strategy, either for maintenance or complete break strategies. Although, thrombocytosis is confirmed as a marker of poor prognosis, it is not predictive of poor outcome for patients treated with intermittent therapy. An intermittent chemotherapy strategy can therefore be applied irrespective of baseline platelet count and does not result in inferior OS compared to continuous chemotherapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Publisher: Elsevier
ISSN: 0305-7372
Date of First Compliant Deposit: 24 June 2021
Date of Acceptance: 15 May 2021
Last Modified: 21 May 2022 17:24
URI: https://orca.cardiff.ac.uk/id/eprint/141470

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