122548-143

Analysis of KRAS/NRAS mutations in phase 3 study 20050181 of panitumumab (pmab) plus FOLFIRI versus FOLFIRI for second-line treatment (tx) of metastatic colorectal cancer (mCRC).

Category: 
Cancers of the Colon and Rectum
Session Type and Session Title: 
General Poster Session C: Cancers of the Colon and Rectum
Oral Abstract Session: Cancers of the Colon and Rectum (eQ&A)
Abstract Number: 
LBA387
Citation: 
J Clin Oncol 32, 2014 (suppl 3; abstr LBA387)
Author(s): 
Marc Peeters, Kelly S. Oliner, Timothy Jay Price, Andres Cervantes, Alberto F. Sobrero, Michel Ducreux, Yevhen Hotko, Thierry Andre, Emily Chan, Florian Lordick, Cornelis J. A. Punt, Andrew Strickland, Gregory Wilson, Tudor-Eliade Ciuleanu, Laslo Roman, Eric Van Cutsem, Ying Tian, Andre Scott Jung, Roger Sidhu, Scott D. Patterson; Department of Oncology, Antwerp University Hospital, Edegem, Belgium; Medical Sciences, Amgen Inc., Thousand Oaks, CA; The Queen Elizabeth Hospital and University of Adelaide, Woodville, Australia; Hospital Clínico, University of Valencia, Valencia, Spain; IRCCS Ospedale San Martino IST, Genova, Italy; Institut Gustave Roussy, Villejuif, France; Uzhgorod National University, Uzhgorod, Ukraine; Hôpital Saint-Antoine, Paris, France; Vanderbilt University Medical Center, Nashville, TN; University Cancer Center Leipzig, University Clinic Leipzig, Leipzig, Germany; Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Monash Medical Centre, East Bentleigh, Australia; Christie Hospital, Manchester, United Kingdom; Prof. Dr. Ion Chiricuta Institute of Oncology, Department of Medical Oncology, Cluj-Napoca, Romania; State Institution of Public Health, Leningrad Regional Oncology Dispensary, St. Petersburg, Russia; UZ Leuven, Gasthuisberg Campus, Leuven, Belgium; Amgen, Inc., Thousand Oaks, CA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: Previously, this study showed significant improvement in progression-free survival (PFS) in pmab + FOLFIRI vs FOLFIRI (HR=0.73; 95% CI: 0.59-0.90; p=0.004) and a trend toward improved overall survival (OS; HR=0.85; 95% CI: 0.70-1.04; P=0.12; Peeters et al. JCO 2010). Recently, analysis from 1st-line mCRC PRIME study showed that mutations in RAS genes (KRAS/NRAS exons 2/3/4) predicted a lack of response to pmab (Douillard et al. NEJM 2013). Methods: The primary objective was to assess the tx effect of pmab + FOLFIRI vs FOLFIRI on OS and PFS based on RAS mutation status in the primary analysis population. Bidirectional Sanger sequencing was used to detect mutations in KRAS exons 3, 4 and NRAS exons 2, 3, 4 in patients (pts) with known WT KRAS exon 2 mCRC. Results: In this prospective retrospective analysis, overall RAS ascertainment rate was 85% (n=1008/1186). 18% of the WT KRAS exon 2 pts harbored additional RAS mutations (n=107/597). Efficacy is shown (Table). Tx HR for pts with WT RAS was 0.803 (95% CI: 0.629-1.024; P=0.077) for OS and 0.695 (95% CI: 0.536-0.903; P=0.006) for PFS. Conclusions: Improvements were observed in the tx effect of pmab + FOLFIRI vs FOLFIRI on OS and PFS in the WT RAS group vs the WT KRAS exon 2 group. Pts with MT RAS mCRC are unlikely to benefit by the addition of pmab to FOLFIRI, similar to pts with MT KRAS exon 2 mCRC in this study. These findings are consistent with previously reported outcomes by RAS status and support RAS testing to determine potentially appropriate pts for pmab tx. Clinical trial information: NCT00339183.

Pmab + FOLFIRI
(N = 303)
FOLFIRI
(N = 294)
HR
(95% CI)
Descriptive
p value
WT RAS,a n 204 211
Median OS - mos
95% CI
16.2
14.5, 19.7
13.9
11.9, 16.1
0.803
0.629, 1.024
0.077
Median PFS - mos
95% CI
6.4
5.5, 7.4
4.4
3.7, 5.5
0.695
0.536, 0.903
0.006
MT RAS,b n 299 294
Median OS - mos
95% CI
11.8
10.4, 13.1
11.1
10.2, 12.4
0.914
0.759, 1.101
0.345
Median PFS - mos
95% CI
4.8
3.7, 5.5
4.0
3.6, 5.5
0.861
0.705, 1.053
0.144
WT KRAS exon 2
MT RAS,c n
61 46
Median OS - mos
95% CI
11.3
8.3, 13.1
9.2
7.0, 12.9
0.825
0.527, 1.293
0.402
Median PFS - mos
95% CI
3.7
2.3, 5.8
3.7
2.8, 5.1
0.892
0.561, 1.419
0.627

a WT in KRAS and NRAS exons 2, 3, and 4. b MT in any KRAS or NRAS exon 2, 3, or 4. c MT in KRAS exon 3 or 4 or NRAS exon 2, 3, or 4.