Peyerl Hanna, Kreye Gudrun, Pecherstorfer Martin, Singer Josef
Karl Landsteiner University of Health Sciences, A-3500 Krems, Austria.
Department of Internal Medicine II, University Hospital Krems, A-3500 Krems, Austria.
Mol Clin Oncol. 2024 Nov 21;22(1):10. doi: 10.3892/mco.2024.2805. eCollection 2025 Jan.
Colorectal cancer (CRC) is one of the most frequent malignancies and, despite screening programs, it is often diagnosed at late stages. Although current first- and second-line therapies stratify for KRAS/NRAS/BRAF mutations, microsatellite instability, tumour location and co-morbidities, the therapeutic mainstay for the first- and second-line treatment of the majority of patients consists of 5-fluorouracil (5-FU)-based chemo-immunotherapy. The present study evaluated the responses of patients with stage IV CRC, treated at the University Hospital Krems between January 1, 2015 and December 31, 2021, who received at least two therapy lines (n=49), with the aim of investigating whether the response to first-line therapy could predict the response to second-line therapy. All patients with first-line complete response (CR) had at least stable disease in response to second-line treatment [overall response rate (ORR)=66.6%]. On the other hand, all patients with progressive disease (PD) in response to first-line treatment (n=7) did not respond to second-line therapy (ORR=0%). These findings also translated to overall survival (OS): Patients with first-line CR had a median OS time of 80 months, whereas patients with PD had a median OS time of 12 months (P<0.001). Furthermore, different parameters were analysed for their impact on OS; the results revealed that BRAF alterations were associated with poor prognosis. Other factors (sex, tumor sidedness, KRAS and MSS/MSI status) had in this cohort no significant effect on OS. In conclusion, the present study demonstrated that, with current treatment strategies applying 5-FU-based chemo-immunotherapy as first- and second-line treatment for patients with metastatic CRC, response to first-line therapy may be a strong predictor for the response to second-line therapy and OS. By exchanging the chemotherapeutic combination partner from oxaliplatin to irinotecan or vice versa, plus the additive anti-epidermal growth factor receptor/anti-vascular endothelial growth factor antibody, the negative factor of non-response to first-line therapy could not be overcome by second-line treatment in this study population. These findings must be confirmed in larger studies, but indicate the need for novel treatment options, especially for patients not responding to first-line 5-FU-based chemo-immunotherapy.
结直肠癌（CRC）是最常见的恶性肿瘤之一，尽管有筛查项目，但它往往在晚期才被诊断出来。尽管目前的一线和二线治疗根据KRAS/NRAS/BRAF突变、微卫星不稳定性、肿瘤位置和合并症进行分层，但大多数患者一线和二线治疗的主要手段是基于5-氟尿嘧啶（5-FU）的化学免疫疗法。本研究评估了2015年1月1日至2021年12月31日在克雷姆斯大学医院接受治疗、接受至少两线治疗的IV期CRC患者（n=49）的反应，目的是调查一线治疗的反应是否可以预测二线治疗的反应。所有一线完全缓解（CR）的患者在二线治疗中至少病情稳定[总缓解率（ORR）=66.6%]。另一方面，所有一线治疗出现疾病进展（PD）的患者（n=7）对二线治疗均无反应（ORR=0%）。这些发现也转化为总生存期（OS）：一线CR的患者中位OS时间为80个月，而PD患者的中位OS时间为12个月（P<0.001）。此外，分析了不同参数对OS的影响；结果显示BRAF改变与预后不良相关。在该队列中，其他因素（性别、肿瘤部位、KRAS和MSS/MSI状态）对OS没有显著影响。总之，本研究表明，对于转移性CRC患者，采用基于5-FU的化学免疫疗法作为一线和二线治疗的当前治疗策略，一线治疗的反应可能是二线治疗反应和OS的有力预测指标。在本研究人群中，通过将化疗联合搭档从奥沙利铂换成伊立替康或反之，再加上添加抗表皮生长因子受体/抗血管内皮生长因子抗体，一线治疗无反应的负面因素无法被二线治疗克服。这些发现必须在更大规模的研究中得到证实，但表明需要新的治疗选择，特别是对于对一线基于5-FU的化学免疫疗法无反应的患者。
