肿瘤

口服卡培他滨(cp)维持治疗与主动监测治疗转移性结直肠癌(mCRC)患者在一线治疗 16 周后稳定或有反应:来自随机 FOCUS4-N 试验的结果

作者:会飞的大胖纸 来源:医学论坛网 日期:2021-06-30
导读

         背景:有大量的随机证据支持在 mCRC 中使用治疗间歇期,但尽管毒性降低,但治疗间歇期并不普遍适用于患者,对 OS 没有损害。先前的试验表明,Cp 和 bevacizumab(贝伐珠单抗)联合应用可延长 PFS,但不能延长 OS。FOCUS4-N 探讨了一线治疗疾病控制患者的口服维持 CP单一疗法。 Background: There is extensive randomised evide

关键字:  肿瘤 

背景:有大量的随机证据支持在 mCRC 中使用治疗间歇期,但尽管毒性降低,但治疗间歇期并不普遍适用于患者,对 OS 没有损害。先前的试验表明,Cp 和 bevacizumab(贝伐珠单抗)联合应用可延长 PFS,但不能延长 OS。FOCUS4-N 探讨了一线治疗疾病控制患者的口服维持 CP单一疗法。


Background: There is extensive randomised evidence supporting the use of treatment breaks in mCRC, but breaks from treatment are not universally offered to patients despite reductions in toxicity, without detriment to OS. Prior trials have shown that the combination of Cp and bevacizumab extend PFS but not OS. FOCUS4-N explores oral maintenance Cp monotherapy in patients with disease control on first line therapy.

 

方法:FOCUS4 是一个分子分层试验项目,登记来自英国 88 家医院的新诊断 mCRC 患者。在接受 16 周一线治疗的同时,一份肿瘤样本被送往实验室检测,以将其疾病分为分子亚型:MSI、BRAF、PIK3CA、TP53 和 RAS 突变。对于某些分子组,有一个靶向治疗亚试验可用,但 FOCUS4-N 试验提供给那些没有靶向亚试验的人。患者被随机分为 1:1 维持 Cp 治疗组和 AM 组。主要结果是使用 8 周的 RECIST 报告的 CT 扫描评估 PFS,并以生活质量(EQ5D 8 周)和 OS 作为次要结果。毒性和耐受性在 4 周后进行评估。在进展中,从最低点开始,患者重新开始一线治疗。 Cox 回归通过意向治疗(ITT)评估疗效,并调整肿瘤位置、WHO 状况、转移负担、一线治疗和生物标志物亚型。

 

Methods: FOCUS4 was a molecularly stratified trial programme registering patients with newly diagnosed mCRC from 88 hospitals in the UK. Whilst undergoing 16 wks of first line treatment, a sample of tumour was sent for laboratory testing to stratify their disease into molecular subtypes: MSI, BRAF, PIK3CA, TP53 and RAS mutations. For some molecular groups, a targeted therapy subtrial was available but entry into the FOCUS4-N trial was offered to those in whom a targeted subtrial was unavailable. Patients were randomised 1:1 between maintenance Cp therapy or AM. The primary outcome was PFS assessed using 8-wkly RECIST reported CT scans with quality of life (using EQ5D 8 weekly) and OS as secondary outcomes. Toxicity and tolerability were assessed 4-wkly. On progression, from the nadir, patients recommenced first line treatment. Cox regression was used to assess efficacy by intention-to-treat (ITT) with adjustment for tumour location, WHO status, metastatic burden, first line treatment and biomarker subtype.

 

结果:2014 年 3 月至 2020 年 3 月,254 名患者被随机分组(127 名为 Cp,127 名为 AM)。两组的基线特征是平衡的,但 AM 组的事件发生率高于预期最后的分析是由于 COVID-19 大流行的停止招募而提前触发的。下表列出了全氟辛烷磺酸和全氟辛烷磺酸的结果。治疗依从性良好,方案分析结果与 ITT 非常相似(PFS HR=0.38(95%CI 0.28-0.51))。毒性从 Cp 到 AM,与预期一样,出现 G$2 疲劳(25%v 12%)、腹泻(23%v 13%)和手足综合征(26%v 3%)。两组患者的生活质量无统计学差异。

 

Results: Between March 2014 and March 2020, 254 patients were randomised (127 to Cp and 127 to AM). Baseline characteristics were balanced between groups but event rates were higher than anticipated in the AM group and the final analysis was triggered early as a result of the COVID-19 pandemic halting recruitment. The table presents results for PFS and OS. Compliance with treatment was good with per-protocol analysis results very similar to ITT (PFS HR=0.38 (95% CI 0.28-0.51)). Toxicity from Cp v AM was as expected with G≥2 fatigue (25% v 12%), diarrhoea (23% v 13%) and hand-foot syndrome (26% v 3%). Quality of life showed no statistically significant differences between the two arms.

 

结论:尽管有强有力的证据表明维持治疗延长了 PFS,但 OS 仍不受影响,FOCUS4-N 为稳定或对 mCRC 一线治疗反应良好的患者提供了额外的证据,以支持使用治疗间歇作为安全的管理选择。不含贝伐单抗的 Cp 可用于在联合治疗 16 周后的间隔期内治疗 PFS。

 

Conclusions: Despite strong evidence of prolongation of PFS with maintenance therapy, OS remains unaffected and FOCUS4-N provides additional evidence to support the use of treatment breaks as a safe management alternative for patients who are stable or responding well to first line treatment for mCRC. Cp without bevacizumab may be used to extend PFS, in the interval after 16 weeks of combination therapy.

 

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