A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer

作者：Kim Tae Won^*; Elme Anneli; Kusic Zvonko; Park Joon Oh; Udrea Anghel Adrian; Kim Sun Young; Ahn Joong Bae; Villalobos Valencia Ricardo; Krishnan Srinivasan; Bilic Ante; Manojlovic Nebojsa; Dong Jun; Guan Xuesong; Lofton Day Catherine; Jung A Scott; Vrdoljak Eduard

来源：British Journal of Cancer, 2016, 115(10): 1206-1214.

DOI：10.1038/bjc.2016.309

• gastrointestinal cancer
• colorectal
• phase 3 trial
• panitumumab

Background: We assessed the treatment effect of panitumumab plus best supportive care (BSC) vs BSC on overall survival (OS) in patients with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC) and report the first prospective extended RAS analysis in a phase 3 trial.
Methods: Patients with wild-type KRAS exon 2 mCRC were randomised 1 : 1 to panitumumab (6mgkg(-1) Q2W) plus BSC or BSC. On-study crossover was prohibited. RAS mutation status was determined by central laboratory testing. The primary endpoint was OS in wild-type KRAS exon 2 mCRC; OS in wild-type RAS mCRC (KRAS and NRAS exons 2, 3, and 4) was a secondary endpoint.
Results: Three hundred seventy seven patients with wild-type KRAS exon 2 mCRC were randomised. Median OS was 10.0 months with panitumumab plus BSC vs 7.4 months with BSC (HR = 0.73; 95% CI = 0.57-0.93; P = 0.0096). RAS ascertainment was 86%. In wild-type RAS mCRC, median OS for panitumumab plus BSC was 10.0 vs 6.9 months for BSC (HR = 0.70; 95% CI = 0.53-0.93; P = 0.0135). Patients with RAS mutations did not benefit from panitumumab (OS HR = 0.99; 95% CI = 0.49-2.00). No new safety signals were observed.
Conclusions: Panitumumab significantly improved OS in wild-type KRAS exon 2 mCRC. The effect was more pronounced in wildtype RAS mCRC, validating previous retrospective analyses.

• 出版日期2016-11-8
• 单位中国人民解放军军事医学科学院