Cardiff University and Velindre Cancer Centre, United Kingdom.
University Medical Center, Utrecht, the Netherlands.
Cancer Treat Rev. 2021 Sep;99:102226. doi: 10.1016/j.ctrv.2021.102226. Epub 2021 May 19.
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.
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.
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).
The highest levels of evidence from this IPDMA 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.
在晚期结直肠癌（aCRC）患者中进行间歇性全身抗癌治疗可能会提高生活质量，而不会影响总生存期（OS）。我们旨在使用来自多个评估间歇性策略的随机对照试验的个体患者数据荟萃分析（IPDMA）为临床实践提供信息。我们还旨在验证血小板增多症作为预测生物标志物是否可以识别接受完全治疗中断的 OS 显著降低的患者。
对间歇性策略对生存的影响进行了 IPDMA 分析，包括所有有数据的相关试验。间歇性策略分为两组：所有治疗完全停止的计划停药策略（6 项试验；2907 例患者）或省略奥沙利铂的同种治疗维持策略（3 项试验；1271 例患者）。主要分析样本是成功完成诱导治疗的患者。此外，还对血小板增多症在连续和间歇性策略下对生存的预测价值进行了预先计划的分析。
所有试验均具有相似的纳入标准。与连续治疗相比，间歇性治疗的总体 IPDMA 并未降低 OS（HR=1.03 [95%CI 0.93-1.14]），无论是完全停药（HR 1.04 [95%CI 0.87-1.26]）还是维持策略（HR 0.99 [95%CI 0.87-1.13]）。血小板增多症被确认为结直肠癌不良预后的标志物，但不能预测治疗中断策略的 OS 受损（与连续治疗相比，交互 HR=0.97 [95%CI 0.66-1.40]）。
这项 IPDMA 提供的最高证据水平表明，接受间歇性治疗策略的患者的生存没有受到损害，无论是维持策略还是完全停药策略。尽管血小板增多症被确认为不良预后的标志物，但它不能预测接受间歇性治疗的患者的不良结局。因此，无论基线血小板计数如何，都可以应用间歇性化疗策略，并且与连续化疗相比，不会导致 OS 降低。
