Bando Hideaki, Takeda Yuriko, Misumi Toshihiro, Nishikawa Tomomi, Wakabayashi Masashi, Yamazaki Kentaro, Oki Eiji, Douillard Jean-Yves, Punt Cornelis J A, Koopman Miriam, Van Cutsem Eric, Bokemeyer Carsten, Venook Alan P, Lenz Heinz-Josef, Maehara Yoshihiko, Andre Thierry, Shi Qian, de Gramont Aimery, Yoshino Takayuki
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
Department of Data Science, National Cancer Center Hospital East, Chiba, Japan.
JNCI Cancer Spectr. 2025 Apr 30;9(3). doi: 10.1093/jncics/pkaf042.
Early tumor shrinkage and depth of response have emerged as potential prognostic indicators in metastatic colorectal cancer (CRC). However, their associations with overall survival, progression-free survival (PFS), and postprogression survival in patients receiving anti-epidermal growth factor receptor (EGFR) antibodies or bevacizumab remain unclear.
We analyzed 3219 treatment-naive patients with RAS wild-type metastatic CRC from 8 randomized studies (CRYSTAL, OPUS, PRIME, CAIRO2, CALGB80405, WJOG4407G, ATOM, PARADIGM) in the Aid and Research in Digestive Cancerology database. Early tumor shrinkage was defined as a 20% or more reduction in tumor size at 8 ± 2 weeks, whereas depth of response was assessed by maximum tumor shrinkage at nadir. Cox regression models evaluated the associations of early tumor shrinkage and depth of response with overall survival, PFS, and postprogression survival, adjusting for confounders. A 2-sided test was conducted with a significance level of .05.
Early tumor shrinkage and depth of response substantially stratified overall survival, PFS, and postprogression survival outcomes across all treatment groups. Early tumor shrinkage positivity was associated with improved overall survival, PFS, and postprogression survival in anti-EGFR and bevacizumab-based therapies, with a trend toward better outcomes in the anti-EGFR group. The depth of response analysis revealed optimal cutoff values of 0.55 for anti-EGFR-based therapy and 0.47 for bevacizumab-based therapy to achieve a median overall survival of approximately 32 months.
Early tumor shrinkage and depth of response serve as valuable prognostic markers in RAS wild-type metastatic CRC, particularly for patients treated with anti-EGFR antibodies. These findings highlight the potential role of early tumor shrinkage and depth of response in guiding treatment strategies and improving outcomes for patients with CRC.
早期肿瘤缩小和缓解深度已成为转移性结直肠癌（CRC）潜在的预后指标。然而，在接受抗表皮生长因子受体（EGFR）抗体或贝伐单抗治疗的患者中，它们与总生存期、无进展生存期（PFS）和进展后生存期的关联仍不明确。
我们在消化系统肿瘤学辅助与研究数据库中分析了来自8项随机研究（CRYSTAL、OPUS、PRIME、CAIRO2、CALGB80405、WJOG4407G、ATOM、PARADIGM）的3219例初治的RAS野生型转移性CRC患者。早期肿瘤缩小定义为在8±2周时肿瘤大小缩小20%或更多，而缓解深度通过最低点时的最大肿瘤缩小来评估。Cox回归模型评估早期肿瘤缩小和缓解深度与总生存期、PFS和进展后生存期的关联，并对混杂因素进行校正。进行双侧检验，显著性水平为0.05。
早期肿瘤缩小和缓解深度在所有治疗组中显著分层了总生存期、PFS和进展后生存期结局。早期肿瘤缩小阳性与基于抗EGFR和贝伐单抗的治疗中总生存期、PFS和进展后生存期的改善相关，在抗EGFR组中有更好结局的趋势。缓解深度分析显示，基于抗EGFR的治疗的最佳截断值为0.55，基于贝伐单抗的治疗为0.47，以实现约32个月的中位总生存期。
早期肿瘤缩小和缓解深度是RAS野生型转移性CRC中有价值的预后标志物，特别是对于接受抗EGFR抗体治疗的患者。这些发现突出了早期肿瘤缩小和缓解深度在指导治疗策略和改善CRC患者结局方面的潜在作用。
