A Post Hoc Analysis of Older Patients with Metastatic Colorectal Cancer Receiving Oxaliplatin-Based Chemotherapy Plus Bevacizumab: The Randomized Obelics Study.

IF 3.4 3区 医学 Q2 GERIATRICS & GERONTOLOGY
Gerardo Rosati, Maria Carmela Piccirillo, Guglielmo Nasti, Alfonso De Stefano, Chiara Carlomagno, Carmela Romano, Antonino Cassata, Lucrezia Silvestro, Anna Nappi, Franco Perrone, Alfredo Budillon, Antonio Avallone
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引用次数: 0

Abstract

Background: 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).

Objective: 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.

Methods: 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/m2 on day 1, plus capecitabine 1000 mg/m2 twice a day (bid) orally on days 1-10 or levofolinic acid, 200 mg/m2, bolus 5-fluorouracil (5-FU) 400 mg/m2, and a 46-h intravenous infusion of 5-FU 2400 mg/m2, every 14 days; oxaliplatin was discontinued after 12 cycles. The primary end point was the overall response rate (ORR).

Results: 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).

Conclusions: 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.

老年转移性结直肠癌患者接受奥沙利铂化疗加贝伐单抗的事后分析:随机Obelics研究
背景:临床研究的II期试验和亚组分析表明,贝伐单抗加奥沙利铂双重化疗对适合的老年转移性结直肠癌(mCRC)患者有效且耐受。目的:在前瞻性III期OBELICS研究中,评估年龄对随机分配的mCRC患者副反应发生率和疗效的影响。方法:根据年龄(190例< 70岁,40例≥70岁),检索东部肿瘤合作组(ECOG)表现状态(PS)为0 / 1的患者230例。患者接受贝伐单抗5mg /kg治疗,与化疗同日(标准组)或化疗前4天(实验组),第1天给予奥沙利铂85mg /m2,第1-10天口服卡培他滨1000mg /m2,每天两次(bid)或左旋亚油酸200mg /m2, 5-氟尿嘧啶(5- fu) 400mg /m2,静脉输注5- fu 2400mg /m2,每14天一次;12个疗程后停用奥沙利铂。主要终点为总缓解率(ORR)。结果:疗效和毒性分析以汇总形式报告,因为两组之间没有统计学上的显著差异。患者特征在老年和年轻患者之间很好地平衡。两组之间ORR无差异(老年患者为50%,年轻患者为57.9%;P = 0.36)。70岁以下和≥70岁受试者的中位PFS分别为10.8(95%可信区间[CI], 9.9-12.2)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)。前者和后者的中位OS分别为26.2个月(95% CI 23.3-32.7)和23.2个月(95% CI 17.3-35.3),调整后风险比为1.60 (95% CI 1.08-2.37;P = 0.027)。考虑到所有形式的毒性,两组之间最严重的毒性无统计学差异(老年患者为65%,年轻患者为60.6%,p = 0.61)。结论:贝伐单抗加奥沙利铂双重化疗对OBELICS试验中随机分配的老年患者有效,不良事件特征与年轻患者没有不同;没有发现新的安全隐患。该事后分析证实,适合mCRC的老年患者应考虑采用该方案治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Drugs & Aging
Drugs & Aging 医学-老年医学
CiteScore
5.50
自引率
7.10%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Drugs & Aging delivers essential information on the most important aspects of drug therapy to professionals involved in the care of the elderly. The journal addresses in a timely way the major issues relating to drug therapy in older adults including: the management of specific diseases, particularly those associated with aging, age-related physiological changes impacting drug therapy, drug utilization and prescribing in the elderly, polypharmacy and drug interactions.
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