Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; University of Queensland, St Lucia, Brisbane, Queensland, Australia.
Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia.
Clin Colorectal Cancer. 2018 Sep;17(3):e593-e599. doi: 10.1016/j.clcc.2018.05.009. Epub 2018 Jun 1.
The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis.
We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use.
Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P = .57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was < 6 versus > 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26).
Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection.
FIRE-3 研究[5-氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）联合西妥昔单抗与 FOLFIRI 联合贝伐珠单抗一线治疗结直肠癌（CRC）]报告称，一线 FOLFIRI 联合西妥昔单抗与 FOLFIRI 联合贝伐珠单抗的无进展生存期（PFS）相似，但总生存期（OS）有所改善。一种可能的解释是，转移性结直肠癌（mCRC）中最初使用的生物制剂会影响其他治疗的后续疗效。我们试图验证这一假设。
我们对 mCRC 登记处（复发性和晚期结直肠癌的治疗）中接受表皮生长因子受体抑制剂（EGFRIs）二线及以后治疗的 RAS 野生型患者的治疗和结局数据进行了查询。从开始使用 EGFRIs 开始的生存结果取决于之前是否使用过贝伐珠单抗以及停止使用贝伐珠单抗和开始使用 EGFRIs 之间的时间间隔。
在 2061 名患者中，确定了 222 名符合条件的患者，其中 170 名（77%）患者之前接受过贝伐珠单抗治疗，52 名（23%）患者未接受过。从 EGFRIs 开始的 PFS 和 OS 不受先前贝伐珠单抗使用的影响（整个队列中，3.8 与 4.2 个月；风险比 [HR]，1.12；P=.81；9.0 与 9.2 个月；HR，1.19；P=.48），也不受原发肿瘤侧别的影响（左侧 HR，1.07；P=.57；右侧 HR，1.2；P=.52）。当贝伐珠单抗和 EGFRIs 之间的间隔<6 个月与>6 个月时，右侧原发性肿瘤的 PFS 明显更短（中位值，2.2 与 6 个月；HR，2.23；P=.01），而左侧肿瘤无此差异（中位值，4.2 与 5.5 个月；HR，1.12；P=.26）。
先前使用贝伐珠单抗对后续 EGFRIs 的活性没有影响。右侧肿瘤中生物制剂之间时间的明显影响可能反映了患者选择。
