在RAS/BRAF野生型转移性结直肠癌患者中，根据原发肿瘤部位比较基于抗表皮生长因子受体（EGFR）的三线治疗与瑞戈非尼或曲氟尿苷/替匹嘧啶的疗效。
Efficacy of third-line anti-EGFR-based treatment versus regorafenib or trifluridine/tipiracil according to primary tumor site in RAS/BRAF wild-type metastatic colorectal cancer patients.
作者信息
Salvatore Lisa, Bensi Maria, Vivolo Raffaella, Zurlo Ina Valeria, Dell'Aquila Emanuela, Grande Roberta, Anghelone Annunziato, Emiliani Alessandra, Citarella Fabrizio, Calegari Maria Alessandra, Ribelli Marta, Basso Michele, Pozzo Carmelo, Tortora Giampaolo
机构信息
Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
Oncologia Medica, Università Cattolica del Sacro Cuore, Rome, Italy.
出版信息
Front Oncol. 2023 Feb 21;13:1125013. doi: 10.3389/fonc.2023.1125013. eCollection 2023.
BACKGROUND
Right- (R) and left-sided (L) metastatic colorectal cancer (mCRC) exhibit different clinical and molecular features. Several retrospective analyses showed that survival benefit of anti-EGFR-based therapy is limited to RAS/BRAF wt L-sided mCRC patients. Few data are available about third-line anti-EGFR efficacy according to primary tumor site.
METHODS
RAS/BRAF wt patients mCRC treated with third-line anti-EGFR-based therapy versus regorafenib or trifluridine/tipiracil (R/T) were retrospectively collected. The objective of the analysis was to compare treatment efficacy according to tumor site. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), response rate (RR) and toxicity.
RESULTS
A total of 76 RAS/BRAF wt mCRC patients, treated with third-line anti-EGFR-based therapy or R/T, were enrolled. Of those, 19 (25%) patients had a R-sided tumor (9 patients received anti-EGFR treatment and 10 patients R/T) and 57 (75%) patients had a L-sided tumor (30 patients received anti-EGFR treatment and 27 patients R/T). A significant PFS [7.2 vs 3.6 months, HR 0.43 (95% CI 0.2-0.76), p= 0.004] and OS benefit [14.9 vs 10.9 months, HR 0.52 (95% CI 0.28-0.98), p= 0.045] in favor of anti-EGFR therapy vs R/T was observed in the L-sided tumor group. No difference in PFS and OS was observed in the R-sided tumor group. A significant interaction according to primary tumor site and third-line regimen was observed for PFS (p= 0.05). RR was significantly higher in L-sided patients treated with anti-EGFR vs R/T (43% vs. 0%; p <0.0001), no difference was observed in R-sided patients. At the multivariate analysis, third-line regimen was independently associated with PFS in L-sided patients.
CONCLUSIONS
Our results demonstrated a different benefit from third-line anti-EGFR-based therapy according to primary tumor site, confirming the role of L-sided tumor in predicting benefit from third-line anti-EGFR vs R/T. At the same time, no difference was observed in R-sided tumor.
背景
右侧（R）和左侧（L）转移性结直肠癌（mCRC）表现出不同的临床和分子特征。多项回顾性分析表明，基于抗表皮生长因子受体（EGFR）治疗的生存获益仅限于RAS/BRAF野生型左侧mCRC患者。关于根据原发肿瘤部位进行的三线抗EGFR疗效的数据很少。
方法
回顾性收集接受三线抗EGFR治疗与瑞戈非尼或曲氟尿苷/替匹嘧啶（R/T）治疗的RAS/BRAF野生型mCRC患者。分析的目的是比较根据肿瘤部位的治疗疗效。主要终点是无进展生存期（PFS）；次要终点是总生存期（OS）、缓解率（RR）和毒性。
结果
共纳入76例接受三线抗EGFR治疗或R/T治疗的RAS/BRAF野生型mCRC患者。其中，19例（25%）患者为右侧肿瘤（9例接受抗EGFR治疗，10例接受R/T治疗），57例（75%）患者为左侧肿瘤（30例接受抗EGFR治疗，27例接受R/T治疗）。在左侧肿瘤组中，观察到抗EGFR治疗相对于R/T有显著的PFS获益[7.2个月对3.6个月，风险比（HR）0.43（95%置信区间0.2 - 0.76），p = 0.004]和OS获益[14.9个月对10.9个月，HR 0.52（95%置信区间0.28 - 0.98），p = 0.045]。在右侧肿瘤组中，未观察到PFS和OS的差异。观察到根据原发肿瘤部位和三线治疗方案在PFS方面有显著交互作用（p = 0.05）。接受抗EGFR治疗的左侧患者的RR显著高于接受R/T治疗的患者（43%对0%；p <0.0001），右侧患者未观察到差异。在多变量分析中，三线治疗方案与左侧患者的PFS独立相关。
结论
我们的结果表明，根据原发肿瘤部位，三线抗EGFR治疗的获益不同，证实了左侧肿瘤在预测三线抗EGFR治疗相对于R/T的获益方面的作用。同时，右侧肿瘤未观察到差异。
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