115136-132

Analysis of KRAS/NRAS and BRAF mutations in the phase III PRIME study of panitumumab (pmab) plus FOLFOX versus FOLFOX as first-line treatment (tx) for metastatic colorectal cancer (mCRC).

Subcategory: 
Category: 
Gastrointestinal (Colorectal) Cancer
Session Type and Session Title: 
Poster Discussion Session, Gastrointestinal (Colorectal) Cancer
Abstract Number: 
3511
Citation: 
J Clin Oncol 31, 2013 (suppl; abstr 3511)
Author(s): 
Kelly S. Oliner, Jean-Yves Douillard, Salvatore Siena, Josep Tabernero, Ronald L. Burkes, Mario Edmundo Barugel, Yves Humblet, Gyorgy Bodoky, David Cunningham, Jacek Jassem, Fernando Rivera, Ilona Kocáková, Paul Ruff, Maria Blasinska-Morawiec, Martin Smakal, Richard Thomas Williams, Alan Rong, Jeffrey S. Wiezorek, Roger Sidhu, Scott D. Patterson; Amgen, Inc., Thousand Oaks, CA; Centre René Gauducheau, Nantes, France; Azienda Ospedaleria Niguarda Ca' Granda, Milano, Italy; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain; Mount Sinai Hospital, Toronto, ON, Canada; Hospital de Gastroenterología, Buenos Aires, Argentina; Centre du Cancer de l'Universite Catholique de Louvain, Brussels, Belgium; Szent László Hospital, Budapest, Hungary; The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom; Medical University of Gdansk, Department of Oncology and Radiotherapy, Gdansk, Poland; Hospital Universitario Marqués de Valdecilla, Santander, Spain; Masarykuv Onkologicky Ustav, Brno, Czech Republic; University of Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa; Wojewodzki Szpital Specjalistyczny, im. M. Kopernika, Lodz, Poland; Institut Onkologie a Rehabilitace na Plesi s.r.o., Nova Ves pod Plesi, Czech Republic

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: Analysis of a phase III pmab monotherapy study indicated that KRAS and NRAS mutations beyond KRAS exon 2 may be predictive of pmab efficacy (Peeters et al, 2013). Methods: The primary objective of this prospectively defined retrospective analysis of PRIME was to assess the effect of pmab + FOLFOX vs FOLFOX on overall survival (OS) in pts with mCRC based on RAS (KRAS or NRAS) or BRAF mutation status. "Gold standard" bidirectional Sanger sequencing and WAVE-based SURVEYOR Scan Kits from Transgenomic (conducted independently) were used to detect mutations in KRAS exon 3, exon 4; NRAS exon 2, exon 3, exon 4; and BRAF exon 15. Results: RAS ascertainment rate was 90%. Tx HRs for pts with WT RAS were 0.78 (95% CI, 0.62 - 0.99; p = 0.04) for OS (median gain of 5.8 months in the pmab arm) and 0.72 (95% CI, 0.58 - 0.90; p = < 0.01) for PFS. Tx HRs for WT KRAS exon 2/mutant (MT) other RAS were 1.29 (95% CI, 0.79 - 2.10; p = 0.31) for OS and 1.28 (95% CI, 0.79 - 2.07; p = 0.32) for PFS. Tx HRs for pts with WT or MT BRAF were inconsistent with a predictive biomarker (Table). Prognostic effects of the tested biomarkers will be presented. Conclusions: A statistically significant OS benefit was observed in pts with WT RAS mCRC treated with pmab + FOLFOX vs FOLFOX. Pmab is unlikely to benefit pts with any RAS mutations. In this analysis, BRAF mutation had no predictive value. Clinical trial information: NCT00364013.

Pmab + FOLFOX
(N = 320)
FOLFOX
(N = 321)
HR
(95% CI)
Descriptive
p value
WT RASa - n 259 253
Median OS - mos
(95% CI)
26.0
(21.7 - 30.4)
20.2
(17.7 - 23.1)
0.78
(0.62 - 0.99)
0.04
Median PFS - mos
(95% CI)
10.1
(9.3 - 12.0)
7.9
(7.2 - 9.3)
0.72
(0.58 - 0.90)
< 0.01
MT RASb - n 272 276
Median OS - mos
(95% CI)
15.6
(13.4 - 17.9)
19.2
(16.7 - 21.8)
1.25
(1.02 - 1.55)
0.04
Median PFS - mos
(95% CI)
7.3
(6.3 - 7.9)
8.7
(7.6 - 9.4)
1.31
(1.07 - 1.60)
0.01
WT RAS and BRAF - n 228 218
Median OS - mos
(95% CI)
28.3
(23.7 - not estimable)
20.9
(18.4 - 23.8)
0.74
(0.57 - 0.96)
0.02
Median PFS - mos
(95% CI)
10.8
(9.4 - 12.4)
9.2
(7.4 - 9.6)
0.68
(0.54 - 0.87)
< 0.01
MT BRAF - n 24 29
Median OS - mos
(95% CI)
10.5
(6.4 - 18.9)
9.2
(8.0 - 15.7)
0.90
(0.46 - 1.76)
0.76
Median PFS - mos
(95% CI)
6.1
(3.7 - 10.7)
5.4
(3.3 - 6.2)
0.58
(0.29 - 1.15)
0.12

aWT in KRAS and NRAS exons 2, 3, and 4. bMT in any KRAS or NRAS exon 2, 3, or 4.