Rosati Gerardo, Piccirillo Maria Carmela, Nasti Guglielmo, De Stefano Alfonso, Carlomagno Chiara, Romano Carmela, Cassata Antonino, Silvestro Lucrezia, Nappi Anna, Perrone Franco, Budillon Alfredo, Avallone Antonio
Medical Oncology Unit, S. Carlo Hospital, Potenza, Italy.
Clinical Trials Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.
Drugs Aging. 2025 Apr;42(4):353-362. doi: 10.1007/s40266-025-01191-8. Epub 2025 Mar 16.
Phase II trials and subgroup analyses of clinical studies suggest that bevacizumab plus an oxaliplatin-based chemotherapy doublet is effective and tolerable in fit older patients with metastatic colorectal cancer (mCRC).
To evaluate the influence of age on the incidence of side effects and efficacy of this combination in patients with mCRC randomized in the prospective phase III OBELICS study.
In total, 230 patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 out of 1 were retrieved on the basis of age (190 < 70 years and 40 ≥ 70 years). They received bevacizumab 5 mg/kg administered either on the same day as chemotherapy (standard arm) or 4 days before chemotherapy (experimental arm) and oxaliplatin 85 mg/m on day 1, plus capecitabine 1000 mg/m twice a day (bid) orally on days 1-10 or levofolinic acid, 200 mg/m, bolus 5-fluorouracil (5-FU) 400 mg/m, and a 46-h intravenous infusion of 5-FU 2400 mg/m, every 14 days; oxaliplatin was discontinued after 12 cycles. The primary end point was the overall response rate (ORR).
Efficacy and toxicity analyses are reported in aggregate form because there were no statistically significant differences between the two arms. Patient characteristics are well balanced between older and younger patients. No difference in ORR was observed between the two groups (50% for the older patients versus 57.9% for the younger ones; p = 0.36). The median PFS was 10.8 (95% confidence interval [CI], 9.9-12.2) and 11.3 (95% CI 8.3-13.0) months, respectively, for subjects younger than 70 years and those aged ≥ 70 years, with an adjusted hazard ratio (HR) of 1.16 (95% CI 0.80-1.68; p = 0.43). The median OS was 26.2 (95% CI 23.3-32.7) for the former and 23.2 (95% CI 17.3-35.3) months for the latter, respectively, with an adjusted HR of 1.60 (95% CI 1.08-2.37; p = 0.027). Considering all forms of toxicity, the most severe ones were not statistically different between the two groups (65% for the older patients and 60.6% for the younger ones, p = 0.61).
Bevacizumab plus an oxaliplatin-based chemotherapy doublet were effective in older patients randomized in the OBELICS trial, and the adverse event profile was not dissimilar from that of younger patients; no new safety concerns were identified. This post hoc analysis confirms that fit older patients with mCRC should be considered for treatment with this regimen.
临床研究的II期试验及亚组分析表明，对于身体状况适宜的老年转移性结直肠癌（mCRC）患者，贝伐单抗联合以奥沙利铂为基础的双药化疗有效且耐受性良好。
在前瞻性III期OBELICS研究中，评估年龄对随机分组的mCRC患者使用该联合方案后副作用发生率及疗效的影响。
根据年龄（190例＜70岁，40例≥70岁）从总共230例东部肿瘤协作组（ECOG）体能状态（PS）为0或1的患者中进行筛选。患者接受贝伐单抗5mg/kg，在化疗当天给药（标准组）或化疗前4天给药（试验组），奥沙利铂85mg/m²于第1天给药，联合卡培他滨1000mg/m²每日2次口服给药（bid），于第1 - 10天使用，或亚叶酸200mg/m²、5 - 氟尿嘧啶（5 - FU）400mg/m²静脉推注及5 - FU 2400mg/m² 46小时静脉滴注，每14天重复一次；奥沙利铂在12个周期后停用。主要终点为总缓解率（ORR）。
由于两组间无统计学显著差异，故疗效和毒性分析以汇总形式报告。老年和年轻患者的患者特征均衡。两组间ORR无差异（老年患者为50%，年轻患者为57.9%；p = 0.36）。年龄＜70岁和≥70岁受试者的中位无进展生存期（PFS）分别为10.8（95%置信区间[CI]，9.9 - 12.2）个月和11.3（95% CI 8.3 - 13.0）个月，校正风险比（HR）为1.16（95% CI 0.80 - 1.68；p = 0.43）。前者的中位总生存期（OS）为26.2（95% CI 23.3 - 32.7）个月，后者为2
