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)

Konference: 2013 49th ASCO Annual Meeting - účast ČR

Kategorie: Gastrointestinální nádory

Téma: Gastrointestinal (Colorectal) Cancer

Číslo abstraktu: 3511

Autoři: Kelly S. Oliner; Prof. Jean-Yves Douillard, MD, PhD; Salvatore Siena; Josep Tabernero, MD; Prof. Ronald L. Burkes, MD, FRCP; Mario Edmundo Barugel; Yves Humblet; M.D. György Bodoky, Ph.D.; Prof. David Cunningham, MD, FRCP; prof. dr hab. n. med. Jacek Jassem; Fernando Rivera; MUDr. Ilona Kocáková, Ph.D.; Prof. M.D. Paul Ruff; Maria Blasinska-Morawiec; MUDr. Martin Šmakal; Richard Thomas Williams; Alan Rong; Jeffrey S. Wiezorek; Roger Sidhu; Scott D. Patterson, PhD

Plný text abstraktu(odkaz vede na stránky ASCO)

Abstrakt byl publikován rovněž v Supplementu časopisu
J Clin Oncol 31, 2013 (suppl; abstr 3511)

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

26

20,2

0,78

0,04

(95% CI)

(21.7 - 30.4)

(17.7 - 23.1)

(0.62 - 0.99)

Median PFS - mos

10,1

7,9

0,72

< 0.01

(95% CI)

(9.3 - 12.0)

(7.2 - 9.3)

(0.58 - 0.90)

MT RASb - n

272

276

   

Median OS - mos

15,6

19,2

1,25

0,04

(95% CI)

(13.4 - 17.9)

(16.7 - 21.8)

(1.02 - 1.55)

Median PFS - mos

7,3

8,7

1,31

0,01

(95% CI)

(6.3 - 7.9)

(7.6 - 9.4)

(1.07 - 1.60)

WT RAS and BRAF - n

228

218

   

Median OS - mos

28,3

20,9

0,74

0,02

(95% CI)

(23.7 - not estimable)

(18.4 - 23.8)

(0.57 - 0.96)

Median PFS - mos

10,8

9,2

0,68

< 0.01

(95% CI)

(9.4 - 12.4)

(7.4 - 9.6)

(0.54 - 0.87)

MT BRAF - n

24

29

   

Median OS - mos

10,5

9,2

0,9

0,76

(95% CI)

(6.4 - 18.9)

(8.0 - 15.7)

(0.46 - 1.76)

Median PFS - mos

6,1

5,4

0,58

0,12

(95% CI)

(3.7 - 10.7)

(3.3 - 6.2)

(0.29 - 1.15)

Datum přednesení příspěvku: 31. 5. 2013