Department of Medicine III, University Hospital, Ludwig Maximilian University (LMU), Munich, Germany.
Gesundheitszentrum St. Marien, Amberg, Germany.
Br J Cancer. 2021 Feb;124(3):587-594. doi: 10.1038/s41416-020-01140-9. Epub 2020 Nov 6.
Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.
The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated.
Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours.
FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases. CLINICALTRIALS.
NCT00433927.
在 FIRE-3 试验中，西妥昔单抗联合 FOLFIRI 方案相较于贝伐珠单抗联合 FOLFIRI 方案在 KRAS 野生型转移性结直肠癌（mCRC）患者中改善了总生存期，但在无进展生存期方面未发现获益。本分析旨在确定在 RAS 野生型 mCRC 患者中接受一线 FOLFIRI 治疗时，西妥昔单抗是否优于贝伐珠单抗，以及原发肿瘤侧位对结局的影响。
意向治疗人群纳入了 593 例 KRAS 外显子 2 野生型 mCRC 患者。进一步的检测确定了 400 例扩展 RAS 野生型疾病患者；其中，352 例（88%）接受了至少 3 个周期的治疗，并且在基线后有≥1 次扫描，可评估反应，构成方案人群（169 例接受西妥昔单抗治疗，183 例接受贝伐珠单抗治疗）。患者接受 5-氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）联合西妥昔单抗或贝伐珠单抗治疗，贝伐珠单抗每两周给药 1 次，于每 14 天周期的第 1 天给药，直至出现缓解、进展或毒性。主要终点是方案人群中的客观缓解率（ORR）。次要终点包括总生存期（OS）和无进展生存期（PFS）。评估了原发肿瘤位置的影响。
在 RAS 野生型人群中，中位 OS 分别为西妥昔单抗组和贝伐珠单抗组的 31 个月和 26 个月（HR 0.76，P=0.012）。在方案人群中，西妥昔单抗组的 ORR（77% vs. 65%，P=0.014）和中位 OS（33 个月 vs. 26 个月，HR 0.75，P=0.011）均优于贝伐珠单抗组，而两组的 PFS 无差异。西妥昔单抗的优势仅出现在左侧肿瘤患者中。
在左侧肿瘤患者中，FOLFIRI 联合西妥昔单抗较 FOLFIRI 联合贝伐珠单抗显著提高了 ORR 和 OS。西妥昔单抗相关的更高反应率可能特别有利于有症状肿瘤或边界可切除转移灶的患者。临床试验。
NCT00433927。
