在三项随机的帕尼单抗试验中，对接受治疗的RAS野生型转移性结直肠癌患者，评估早期肿瘤缩小和缓解深度对生存结果影响的探索性分析。

Exploratory analyses assessing the impact of early tumour shrinkage and depth of response on survival outcomes in patients with RAS wild-type metastatic colorectal cancer receiving treatment in three randomised panitumumab trials.

作者信息

Taieb Julien, Rivera Fernando, Siena Salvatore, Karthaus Meinolf, Valladares-Ayerbes Manuel, Gallego Javier, Geissler Michael, Koukakis Reija, Demonty Gaston, Peeters Marc

机构信息

Department of Hepatogastroenterology and GI Oncology, Georges Pompidou European Hospital and Sorbonne Paris Cité / Université Paris Descartes, 20 rue Leblanc, 75015, Paris, France.

Hospital Universitario Marqués de Valdecilla, Santander, Spain.

出版信息

J Cancer Res Clin Oncol. 2018 Feb;144(2):321-335. doi: 10.1007/s00432-017-2534-z. Epub 2017 Oct 28.

PURPOSE

To report exploratory analyses of early tumour shrinkage (ETS) and depth of response (DpR) in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), receiving the first-line treatment in three randomised panitumumab trials.

METHODS

Data from the PRIME (NCT00364013), PEAK (NCT00819780) and PLANET (NCT00885885) studies were included. Median DpR, the proportion of patients achieving ETS ≥ 20% or ≥ 30% at week 8, and the impact of ETS and DpR (including by category) on outcome were analysed. Factors associated with ETS and DpR and the optimal ETS/DpR cut-off values for predicting improved overall survival (OS) were assessed.

RESULTS

Overall, 505, 170 and 53 patients had RAS WT mCRC in PRIME, PEAK and PLANET, respectively. Patients receiving panitumumab had higher ETS rates (≥ 30%: PRIME 59% vs. 38%; PEAK 64% vs. 45%) and greater DpR (PRIME: 54% vs. 46%; PEAK: 65% vs. 46%) than those receiving treatment without panitumumab. In multiple regression analyses, panitumumab treatment, liver-only metastases and WT BRAF status were consistently associated with improved ETS and DpR outcomes. Irrespective of treatment, ETS and DpR were associated with improved progression-free survival, overall survival and resection rates; most resections occurred in patients in the two highest DpR categories. In PRIME and PEAK, respectively, the optimal cut-offs for predicting improved OS were 32 and 34% for ETS, and 59 and 70% for DpR.

CONCLUSIONS

These exploratory analyses suggest that panitumumab is associated ETS and DpR benefits in patients with RAS WT mCRC and that achieving these endpoints during first-line treatment is linked with favourable outcomes.

目的

报告在三项帕尼单抗随机试验中接受一线治疗的RAS野生型（WT）转移性结直肠癌（mCRC）患者的早期肿瘤缩小（ETS）和缓解深度（DpR）的探索性分析。

方法

纳入PRIME（NCT00364013）、PEAK（NCT00819780）和PLANET（NCT00885885）研究的数据。分析中位DpR、在第8周达到ETS≥20%或≥30%的患者比例，以及ETS和DpR（包括按类别）对结局的影响。评估与ETS和DpR相关的因素以及预测改善总生存期（OS）的最佳ETS/DpR临界值。

结果

总体而言，PRIME、PEAK和PLANET研究中分别有505例、170例和53例患者患有RAS WT mCRC。接受帕尼单抗治疗的患者比未接受帕尼单抗治疗的患者具有更高的ETS率（≥30%：PRIME为59%对38%；PEAK为64%对45%）和更大的DpR（PRIME：54%对46%；PEAK：65%对46%）。在多元回归分析中，帕尼单抗治疗、仅肝转移和BRAF WT状态始终与改善的ETS和DpR结局相关。无论治疗如何，ETS和DpR均与改善的无进展生存期、总生存期和切除率相关；大多数切除发生在DpR最高的两个类别的患者中。在PRIME和PEAK研究中，预测改善OS的ETS最佳临界值分别为32%和34%，DpR最佳临界值分别为59%和70%。