年龄和性别对转移性结直肠癌化疗联合贝伐珠单抗的安全性和疗效的影响：TRIBE 和 TRIBE2 研究的 pooled 分析。
Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies.
机构信息
Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa.
Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Veneto Institute of Oncology - IRCCS, Padova.
出版信息
Ann Oncol. 2019 Dec 1;30(12):1969-1977. doi: 10.1093/annonc/mdz403.
BACKGROUND
The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender.
PATIENTS AND METHODS
Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates.
RESULTS
Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%).
CONCLUSIONS
The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.
背景
TRIBE 和 TRIBE2 三期研究将转移性结直肠癌患者随机分为一线 FOLFOXIRI/贝伐珠单抗或双药（FOLFIRI 或 FOLFOX）/贝伐珠单抗。这两项研究表明，三联疗法在增加化疗相关不良反应（AE）发生率的情况下，显著提高了疗效。在这两项试验中，年龄在 18 岁至 70 岁之间且 ECOG PS 评分为 2 分及以下、年龄在 71 岁至 75 岁之间且 ECOG PS 评分为 0 分的男性和女性患者均符合条件。我们根据年龄和性别对 FOLFOXIRI/贝伐珠单抗与双药/贝伐珠单抗的疗效进行了亚组分析。
方法
根据年龄（<70 岁与 70-75 岁）和性别进行了亚组分析，评估了总缓解率（ORR）、无进展生存期（PFS）和 AE 发生率。
结果
在 1187 例患者中，1005 例（85%）年龄<70 岁，182 例（15%）年龄 70-75 岁；693 例（58%）为男性，494 例（42%）为女性。在 ORR 和 PFS 方面，年龄或性别与强化一线化疗的获益之间没有证据表明存在交互作用，也没有证据表明强化一线化疗会增加发生 G3/4AE 的风险。老年患者和女性患者的总体 G3/4AE 发生率更高（73%比 60%，P<0.01；69%比 57%，P<0.01）。值得注意的是，在 FOLFOXIRI/贝伐珠单抗组中，分别有 27%和 16%的老年患者发生 G3/4 级腹泻和发热性中性粒细胞减少症，而女性患者报告了较高的任何级别恶心（67%）和呕吐（50%）发生率。
结论
与双药/贝伐珠单抗相比，FOLFOXIRI/贝伐珠单抗在 ORR 和 PFS 方面的改善与性别和年龄无关，在老年患者和女性患者中，AE 发生率也有相似的相对增加。在接受 FOLFOXIRI/贝伐珠单抗治疗的年龄在 70-75 岁的患者中，应建议初始剂量减少，并且可能需要一级 G-CSF 预防；应考虑对女性患者进行更仔细的止吐预防。
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