Division of Medical Oncology, New York University, New York, NY.
SWOG Statistics and Data Management Center, Seattle, WA.
Clin Colorectal Cancer. 2018 Mar;17(1):e121-e125. doi: 10.1016/j.clcc.2017.10.008. Epub 2017 Oct 24.
Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer.
Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients.
induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%.
Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%).
Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting.
新辅助放化疗（NCRT）是局部晚期直肠癌的标准治疗方法。病理完全缓解（pCR）与生存改善相关。在现代 III 期 NCRT 试验中，pCR 范围为 10%-20%。西妥昔单抗可提高 KRAS（KRAS 原癌基因）野生型（wt）转移性结直肠癌的反应。S0713 旨在评估在诱导化疗和 NCRT 中额外使用西妥昔单抗对局部晚期、KRAS-wt 直肠癌的 pCR 改善。
患者入选标准：经活检证实的 II 期至 III 期，KRAS-wt 直肠腺癌；无肠梗阻；足够的血液学、肝脏和肾功能；表现状态为 0-2 级。目标入组人数：80 例患者。
诱导化疗采用 wCAPOX（每周卡培他滨和奥沙利铂）和西妥昔单抗，随后采用相同方案联合放疗（省略第 15 天的奥沙利铂）。如果在 40 例患者接受所有治疗后计划的中期分析中观察到少于 7 例 pCR，则研究将结束。如果真实的 pCR 率>35%，在显著性为 0.04 的情况下，80 名合格患者将提供 90%的效能。如果 pCR 概率≤20%，则该方案将缺乏未来的意义。
2009 年 2 月至 2013 年 4 月期间，共有 83 例患者注册。其中 4 例不合格，4 例未治疗，因此 75 例可评估临床结局和毒性，其中 65 例接受了手术。在 75 例患者中，20 例（27%；95%置信区间[CI]，17%-38%）达到 pCR；19 例（25%）有显微镜下的癌症；36 例（48%）有轻微/无反应（包括 10 例未手术）。3 年无疾病生存率为 73%（95%CI，63%-83%）。
我们的试验未达到 35%的 pCR 目标。毒性通常是可以接受的。该方案不能在临床试验之外推荐。
