You are here
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.
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 + BSC||BSC||HR or OR|
|WT KRAS exon 2, n||189||188|
|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, n||142||128|
|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.
Abstracts by Tae Won Kim:
A multinational, randomized, phase III trial of XELIRI (+bevacizumab) versus FOLFIRI (+bevacizumab) as the second-line chemotherapy for metastatic colorectal cancer: Asian XELIRI project (AXEPT).Meeting: 2016 Gastrointestinal Cancers Symposium | Abstract No: TPS780
Analysis of plasma protein biomarkers from the phase 3 CONCUR study of regorafenib in Asian patients with metastatic colorectal cancer (mCRC).Meeting: 2016 Gastrointestinal Cancers Symposium | Abstract No: 672