Capecitabine Versus Active Monitoring in Stable or Responding Metastatic Colorectal Cancer After 16 Weeks of First-Line Therapy: Results of the Randomized FOCUS4-N Trial.
Capecitabine Versus Active Monitoring in Stable or Responding Metastatic Colorectal Cancer After 16 Weeks of First-Line Therapy: Results of the Randomized FOCUS4-N Trial.
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DOI：
10.1200/jco.21.01436
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发表时间：
2021-11-20
期刊：
影响因子：
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通讯作者：
FOCUS4 Trial Investigators
中科院分区：
文献类型：
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作者：
Adams RA;Fisher DJ;Graham J;Seligmann JF;Seymour M;Kaplan R;Yates E;Parmar M;Richman SD;Quirke P;Butler R;Brown E;Collinson F;Falk S;Wasan H;Shiu KK;Middleton G;Samuel L;Wilson RH;Brown LC;Maughan TS;FOCUS4 Trial Investigators
尽管有大量随机证据支持在转移性结直肠癌（mCRC）中使用治疗中断，但尽管在不损害总生存期（OS）的情况下改善了生活质量，但并未普遍提供给患者。建立FOX 4-N以探索口服维持治疗对一线治疗有反应的患者的影响。FOCR 4是一项分子分层试验项目，登记了新诊断的mCRC患者。FOCUS 4-N试验提供给无法进行目标子试验或生物标志物测试失败的患者。使用1：1的比例将患者随机分配至卡培他滨维持治疗组和主动监测组（AM）。主要结局是无进展生存期（PFS），次要结局包括OS毒性和耐受性。2014年3月至2020年3月期间，254例患者被随机分配到88个英国研究中心（127例接受卡培他滨治疗，127例接受AM治疗）。基线特征平衡。有强有力的证据表明PFS有效（风险比= 0.40; 95%CI，0.21至0.75; P <0.0001），但OS无显著改善（风险比0.93; 95%CI，0.69至1.27; P = 0.66）。治疗依从性良好，卡培他滨与AM的毒性与预期一致，包括≥ 2级疲乏（25% v12%）、腹泻（23% v13%）和手足综合征（26% v3%）。两组之间的生活质量差异不大。尽管有强有力的证据表明维持治疗可控制疾病，但OS仍不受影响，FOX 4-N提供了额外的证据，支持使用治疗中断作为稳定或对一线治疗有反应的mCRC患者的安全管理替代方案。一线治疗16周后，可使用卡培他滨（不含贝伐珠单抗）延长PFS。
Despite extensive randomized evidence supporting the use of treatment breaks in metastatic colorectal cancer (mCRC), they are not universally offered to patients despite improvements in quality of life without detriment to overall survival (OS). FOCUS4-N was set up to explore the impact of oral maintenance therapy in patients who are responding to first-line therapy. FOCUS4 was a molecularly stratified trial program that registered patients with newly diagnosed mCRC. The FOCUS4-N trial was offered to patients in whom a targeted subtrial was unavailable or biomarker tests failed. Patients were randomly assigned using a 1:1 ratio between maintenance capecitabine and active monitoring (AM). The primary outcome was progression-free survival (PFS) with secondary outcomes including OS toxicity and tolerability. Between March 2014 and March 2020, 254 patients were randomly assigned (127 to capecitabine and 127 to AM) across 88 UK sites. Baseline characteristics were balanced. There was strong evidence of efficacy for PFS (hazard ratio = 0.40; 95% CI, 0.21 to 0.75; P < .0001), but no significant improvement in OS (hazard ratio, 0.93; 95% CI, 0.69 to 1.27; P = .66) was observed. Compliance with treatment was good, and toxicity from capecitabine versus AM was as expected with grade ≥ 2 fatigue (25% v 12%), diarrhea (23% v 13%), and hand-foot syndrome (26% v 3%). Quality of life showed little difference between the groups. Despite strong evidence of disease control with maintenance therapy, OS remains unaffected and FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for mCRC. Capecitabine without bevacizumab may be used to extend PFS in the interval after 16 weeks of first-line therapy.