Petrelli Fausto, Antista Maria, Dottorini Lorenzo, Russo Alessandro, Arru Marcella, Invernizzi Roberta, Manzoni Mariangela, Cremolini Chiara, Zaniboni Alberto, Garrone Ornella, Tomasello Gianluca, Ghidini Michele
Oncology unit, ASST Bergamo Ovest, Treviglio, BG, Italy.
Oncology Unit, ASST Crema, Crema, CR, Italy.
Heliyon. 2024 Aug 22;10(17):e36497. doi: 10.1016/j.heliyon.2024.e36497. eCollection 2024 Sep 15.
The molecular profile of colorectal cancer (CRC) plays a crucial role in understanding patient prognosis and treatment response. Within CRC, a distinct subgroup can be identified by the presence of the BRAF V600E mutation. This specific mutation, classified as Class I of BRAF mutations, is known to be associated with a poor prognosis and resistance to standard therapy. To determine the most effective treatment approach for this specific subgroup of CRC, we conducted a network meta-analysis (NMA) to compare various pharmacological interventions and evaluate their relative effectiveness in BRAF-mutated CRCs.
On July 31, 2023, we conducted a systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Embase. The inclusion criteria were as follows: 1) reporting of outcomes in patients with BRAF-mutated CRC who underwent first-line chemotherapy; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. The data were combined using HRs for overall and progression-free survival (OS and PFS) using random-effects models. NMA was performed under the Bayesian framework, utilizing the GeMTC package. The relative rankings of the treatments were determined using SUCRA scores.
A total of 16 studies were included. When compared to standard chemotherapy (CT) doublets (such as FOLFOX or FOLFIRI), none of the comparison arms demonstrated a gain in OS. CT doublet + bevacizumab did not show significant superiority over either CT doublet alone or 5FU/capecitabine + bevacizumab. FOLFOXIRI and FOLFOXIRI + bevacizumab did not show superiority over any other treatment schedule that was compared. CT doublets + bevacizumab had the highest SUCRA score (0.87), followed by single-agent fluoropyrimidines + bevacizumab (0.61), and FOLFOXIRI (0.56). Regarding PFS, no regimen was found to be superior to the combination of CT doublet plus bevacizumab. However, FOLFOXIRI + bevacizumab + atezolizumab showed a tendency towards better results (HR = 0.26, 95 % CI 0.05-1.1).
Our review suggests that a CT doublet with bevacizumab is the most favorable option for OS. However, a reasonable alternative could be a triplet CT without bevacizumab.
结直肠癌（CRC）的分子特征在理解患者预后和治疗反应方面起着至关重要的作用。在CRC中，可通过BRAF V600E突变的存在识别出一个独特的亚组。这种特定的突变被归类为BRAF突变的I类，已知与预后不良和对标准治疗的耐药性相关。为了确定针对这一特定CRC亚组的最有效治疗方法，我们进行了一项网络荟萃分析（NMA），以比较各种药物干预措施，并评估它们在BRAF突变型CRC中的相对有效性。
2023年7月31日，我们对PubMed、Cochrane对照试验中央注册库和Embase进行了系统检索。纳入标准如下：1）报告接受一线化疗的BRAF突变型CRC患者的结局；2）以风险比（HR）报告生存信息；3）英文发表。使用随机效应模型，将总体生存和无进展生存（OS和PFS）的HR数据合并。在贝叶斯框架下，利用GeMTC软件包进行NMA。使用SUCRA分数确定治疗的相对排名。
共纳入16项研究。与标准化疗（CT）双联方案（如FOLFOX或FOLFIRI）相比，没有一个比较组在OS方面显示出获益。CT双联方案 + 贝伐单抗并不比单独的CT双联方案或5-氟尿嘧啶/卡培他滨 + 贝伐单抗更具优势。FOLFOXIRI和FOLFOXIRI + 贝伐单抗并不比所比较的任何其他治疗方案更具优势。CT双联方案 + 贝伐单抗的SUCRA分数最高（0.87），其次是单药氟嘧啶 + 贝伐单抗（0.61）和FOLFOXIRI（0.56）。关于PFS，没有发现任何方案优于CT双联方案加贝伐单抗的联合方案。然而，FOLFOXIRI + 贝伐单抗 + 阿替利珠单抗显示出有更好结果的趋势（HR = 0.26，95% CI 0.05 - 1.1）。
我们的综述表明，含贝伐单抗的CT双联方案是OS的最有利选择。然而，一个合理的替代方案可能是不含贝伐单抗的三联CT方案。
