Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer
Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer
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DOI：
10.1093/annonc/mdu141
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发表时间：
2014-07-01
影响因子：
50.5
通讯作者：
Sidhu, R.
中科院分区：
文献类型：
--
作者：
Douillard, J. Y.;Siena, S.;Sidhu, R.
Panitumumab联合化疗治疗转移性结直肠癌疗效测定（PRIME）的随机试验表明，Panitumumab -FOLFOX4作为野生型（WT） KRAS转移性结直肠癌（mCRC）的一线治疗，与FOLFOX4相比，可显著提高无进展生存期（PFS），这是该研究的主要终点。患者以1:1的比例随机分配至每2周帕尼珠单抗6.0 mg/kg + FOLFOX4（组1）或FOLFOX4（组2）组。这项预先指定的疗效和安全性的最终描述性分析计划在最后一名患者入组后30个月进行。共有1183名患者被随机分组。WT KRAS mCRC的中位PFS在第1组为10.0个月[95%置信区间（CI） 9.3-11.4个月]，在第2组为8.6个月（95% CI 7.5-9.5个月）；风险比(HR) = 0.80；95% ci 0.67-0.95；P = 0.01。WT KRAS mCRC的中位总生存期（OS）在第1组为23.9个月（95% CI 20.3-27.7个月），在第2组为19.7个月（95% CI 17.6-22.7个月）；Hr = 0.88；95% ci 0.73-1.06；P = 0.17 （68% OS事件）。对更新的生存期（bbb80 % OS事件）进行了探索性分析，表明OS有所改善；Hr = 0.83；95% ci 0.70-0.98；WT KRAS mCRC P = 0.03。不良事件概况与初步分析一致。在WT KRAS mCRC中，PFS得到改善，客观反应更高，并且panitumumab-FOLFOX4有改善OS的趋势，在最新的WT KRAS mCRC患者生存分析中，panitumumab + FOLFOX4与单独FOLFOX4相比，OS有显著改善（P = 0.03）。这些数据支持panitumumab-FOLFOX4对先前未治疗的WT KRAS mCRC患者的正面获益-风险分析。KRAS检测对于选择合适的患者接受帕尼单抗治疗至关重要。
The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study.Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled.A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (> 80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis.In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.