Orillard Emeline, Henriques Julie, Vernerey Dewi, Almotlak Hamadi, Calcagno Fabien, Fein Francine, Fratté Serge, Jary Marine, Klajer Elodie, Vienot Angelique, Borg Christophe, Kim Stefano
Department of Oncology, University Hospital of Besançon, Besançon, France.
Bourgogne Franche-Comté University, INSERM, Établissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France.
Front Oncol. 2022 Mar 7;12:763926. doi: 10.3389/fonc.2022.763926. eCollection 2022.
Studies have reported a beneficial role of the addition of trastuzumab to platin-5-FU based chemotherapy in first-line advanced HER2 positive gastroesophageal adenocarcinoma (GEA). However, the effect of taxanes combined with platin-5FU + trastuzumab (PFT) is understudied.
We performed a retrospective cohort study to evaluate the interest of taxanes among HER2-positive advanced GEA patients treated with PFT. We enrolled HER2-positive advanced GEA patients who underwent treatment between January 2009 to March 2021 in seven hospitals centers in France, treated with PFT alone (S group) or with taxanes + PFT regimen (T group). The primary outcome was progression-free survival (PFS). Also, overall survival (OS), response rate, conversion surgery rate, and safety were evaluated.
Overall, 65 patients received PFT-based therapy, 24 patients in the T group, and 41 patients in the S group. To avoid the selection bias, only those patients presenting an ECOG-PS of 0-1 and synchronous metastasis (21 patients in the T group and 19 patients in the S group) were included for analysis. The median PFS was 9.3 months (95%CI 7.0 to 17.2) in the T group and 5.9 months (95%CI 3.7 to 9.6) in the S group (log-rank p=0.038). Treatment by taxanes was significantly associated with a better PFS in univariate (HR 0.49; 95%CI 0.25 to 0.98, p=0.042) and multivariate Cox regression analysis (HR 0.44; 95%CI 0.21 to 0.94, p=0.033), and IPTW method (HR 0.56; 95% CI 0.34 to 0.91, p=0.019). OS was prolonged (19.0 months (95%CI 7.8 to 45.2) vs 13.0 months (95%CI 5.5 to 14.8), log-rank p=0.033) in favor of the T group. Treatment by taxanes was significantly associated with a better OS in univariate Cox regression analysis (HR 0.49; 95%CI 0.21 to 0.96, p=0.038) and IPTW method (HR 0.49; 95% CI 0.29 to 0.84, p=0.009). The response rate was higher in the T group, with conversion surgery in five patients. No treatment-related death was observed in both groups.
Given the improvement in PFS and OS, the addition of taxanes to standard chemotherapy could be considered as a promising treatment for selected HER2-positive advanced GEA patients, with PS 0-1 and synchronous metastasis (NCT04920747).
研究报告称，在一线晚期人表皮生长因子受体2（HER2）阳性胃食管腺癌（GEA）中，在基于铂类-5-氟尿嘧啶（5-FU）的化疗中添加曲妥珠单抗具有有益作用。然而，紫杉烷类联合铂类-5FU+曲妥珠单抗（PFT）的效果研究较少。
我们进行了一项回顾性队列研究，以评估紫杉烷类在接受PFT治疗的HER2阳性晚期GEA患者中的作用。我们纳入了2009年1月至2021年3月期间在法国7家医院中心接受治疗的HER2阳性晚期GEA患者，这些患者单独接受PFT治疗（S组）或接受紫杉烷类+PFT方案治疗（T组）。主要结局是无进展生存期（PFS）。此外，还评估了总生存期（OS）、缓解率、转化手术率和安全性。
总体而言，65例患者接受了基于PFT的治疗，T组24例，S组41例。为避免选择偏倚，仅纳入那些东部肿瘤协作组体能状态（ECOG-PS）为0-1且有同步转移的患者（T组21例，S组19例）进行分析。T组的中位PFS为9.3个月（95%置信区间[CI]7.0至17.2），S组为5.9个月（95%CI 3.7至9.6）（对数秩检验p=0.038）。在单因素（风险比[HR]0.49；95%CI 0.25至0.98，p=0.042）和多因素Cox回归分析（HR 0.44；95%CI 0.21至0.94，p=0.033）以及逆概率加权（IPTW）法（HR 0.56；95%CI 0.34至0.91，p=0.019）中，紫杉烷类治疗与更好的PFS显著相关。T组的OS延长（19.0个月（95%CI 7.8至45.2）对13.0个月（95%CI 5.5至14.8），对数秩检验p=0.033）。在单因素Cox回归分析（HR 0.49；95%CI 0.21至0.96，p=0.038）和IPTW法（HR 0.49；95%CI 0.29至0.84，p=0.009）中，紫杉烷类治疗与更好的OS显著相关。T组的缓解率更高，有5例患者接受了转化手术。两组均未观察到与治疗相关的死亡。
鉴于PFS和OS的改善，对于选定的ECOG-PS为0-1且有同步转移的HER2阳性晚期GEA患者，在标准化疗中添加紫杉烷类可被视为一种有前景的治疗方法（临床试验注册号：NCT04920747）。
