159907-173

An open label, randomized phase III trial evaluating the treatment (tx) effects of panitumumab (pmab) + best supportive care (BSC) versus BSC in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and in WT RAS mCRC.

Category: 
Cancers of the Colon, Rectum, and Anus
Session Type and Session Title: 
Poster Session C: Cancers of the Colon, Rectum, and Anus
Abstract Number: 

642

Poster Board Number: 
Poster Session C Board #H3
Citation: 
J Clin Oncol 34, 2016 (suppl 4S; abstr 642)
Author(s): 
Tae Won Kim, Anneli Elme, Zvonko Kusic, Joon Oh Park, Anghel Adrian Udrea, Sun Young Kim, Joong Bae Ahn, Ricardo Villalobos Valencia, Krishnan Srinivasan, Ante Bilic, Nebojsa Manojlovic, Jun Dong, Xuesong Guan, Catherine Lofton-Day, A. Scott Jung, Eduard Vrdoljak; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; North Estonia Medical Centre Foundation, Tallinn, Estonia; Clinical Hospital Center, Zagreb, Croatia; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Medisprof S.R.L., Cluj-Napoca, Romania; Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea; Department of Internal Medicine, Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; Hospital De Oncologia Centro Medico Nacional, Mexico City, Mexico; Dr. Rai Memorial Cancer Center, Chennai, India; Klinicka bolnica Sveti Duh, Zagreb, Croatia; Clinic for Gastroenterology and Hepatology of Military Medical Academy of Serbia, Belgrade, Serbia; Amgen, Inc., Thousand Oaks, CA; Clinical Hospital Split, Split, Croatia

Abstract Disclosures

Abstract: 

Background: An overall survival (OS) benefit in WT KRAS exon 2 mCRC was not seen with pmab monotherapy in study 20020408 possibly due to crossover of patients (pts) in the BSC arm. Retrospective analyses have indicated that other KRAS and NRAS mutations beyond KRAS exon 2 are predictive of anti-EGFR tx effects. Study 20100007 assesses the OS benefit of pmab in chemorefractory WT KRAS exon 2 mCRC and is the first phase 3 trial to prospectively evaluate pmab tx effects in WT RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC. Methods: Anti-EGFR naive pts were randomized 1:1 to receive pmab (6 mg/kg Q2W) + BSC or BSC. KRAS exon 2 and RAS mutation status of tumors were determined centrally. The primary endpoint was OS in WT KRAS exon 2 mCRC. Secondary endpoints were OS in WT RAS mCRC and progression-free survival (PFS), objective response rate (ORR), and safety in both WT KRAS exon 2 and WT RAS groups. Crossover was not permitted. Results: 377 pts with WT KRAS exon 2 mCRC were enrolled. RAS ascertainment rate was 86%. OS was significantly improved with pmab + BSC vs BSC in both WT KRAS exon 2 (HR=0.73, 95% CI=0.57-0.93, P=0.0096) and WT RAS (HR=0.70, 95% CI=0.53-0.93, P=0.0135) mCRC (results in table). Pts with mutant RAS mCRC did not benefit from pmab tx (OS HR=0.99, 95% CI=0.49-2.00). No new safety signals were seen. Conclusions: Pmabsignificantly improved OS in chemorefractory WT KRAS exon 2 mCRC. The tx effects in OS and PFS were more pronounced in those with WT RAS mCRC, further substantiating the importance of RAS testing at diagnosis to best inform the use of pmab to treat mCRC. Clinical trial information: NCT01412957

Pmab + BSCBSCHR or OR
(95% CI)
P value
WT KRAS exon 2, n189188
Median OS - mos (95% CI)10.0 (8.7-11.4)7.4 (5.8-9.3)0.73 (0.57-0.93)0.0096
Median PFS - mos (95% CI)3.6 (3.4-5.3)1.7 (1.6-1.9)0.51 (0.41-0.64)<0.0001
ORR – % (95% CI)27.0 (20.8-33.9)1.6 (0.3-4.6)24.9 (7.5-123.8)<0.0001
WT RAS, n142128
Median OS - mos (95% CI)10.0 (8.7-11.6)6.9 (5.2-7.9)0.70 (0.53-0.93)0.0135
Median PFS - mos (95% CI)5.2 (3.5-5.3)1.7 (1.6-2.2)0.46 (0.35-0.59)<0.0001
ORR – % (95% CI)31.0 (23.5-39.3)2.3 (0.5-6.7)20.0 (5.9-101.6)<0.0001

HR=hazard ratio; OR=odds ratio.