Final results from PRIME: Randomized phase III study of panitumumab (pmab) with FOLFOX4 for first line metastatic colorectal cancer (mCRC).

Abstract

3510^ Background: The primary analysis of PRIME demonstrated that pmab + FOLFOX4 significantly improved progression-free survival (PFS) vs FOLFOX4 for 1st line mCRC in patients (pts) with wild-type (WT) KRAS mCRC. Methods: Pts, randomized 1:1 to pmab 6.0 mg/kg every 2 weeks + FOLFOX4 (Arm 1) or FOLFOX4 (Arm 2), had no prior chemotherapy for mCRC, ECOG ≤2, and tumor tissue for biomarker testing. The primary endpoint was PFS by central assessment. Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. KRAS tumor status was determined by a blinded central lab prior to the primary analysis. This prespecified final descriptive analysis of PFS and OS was planned for 30 months (mos) after the last pt was enrolled. Results: 1,183 pts were randomized and received treatment (tx): 593 Arm 1, 590 Arm 2. 1,096/1,183 pts (93%) had KRAS results. Adverse event rates were consistent with the primary analysis. Results are shown (Table). Conclusions: In pts treated in Arm 1, PFS was improved, ORR was higher, and there was a trend toward improved OS in pts with WT KRAS mCRC, and PFS and OS were reduced in pts with mutant (MT) KRAS mCRC. OS was significantly affected by post study EGFR inhibitor use. KRAS testing is critical to select appropriate pts for tx with pmab. WT KRAS mCRC (n = 656) Arm 1 (n = 325) Arm 2 (n = 331) HR (95% CI) P valuea Median PFS - mos (95% CI) 10.0 (9.3 – 11.4) 8.6 (7.5 – 9.5) 0.80 (0.67 – 0.95) 0.009 Median OS - mos (95% CI) 23.9 (20.3 – 27.7) 19.7 (17.6 – 22.7) 0.88 (0.73 – 1.06) 0.17 ORRb - % (95% CI) 57 (51 – 63) 48 (42 – 53) Odds ratio (95% CI) 1.47 (1.07 – 2.04) 0.018 MT KRAS mCRC (n = 440) Arm 1 (n = 221) Arm 2 (n = 219) Median PFS - mos (95% CI) 7.4 (6.9 – 8.1) 9.2 (8.1 – 9.9) 1.27 (1.04 – 1.55) 0.02 Median OS - mos (95% CI) 15.5 (13.1 – 17.6) 19.2 (16.5 – 21.7) 1.17 (0.95 – 1.45) 0.15 ORRb - % (95% CI) 40 (33 – 47) 41 (34 – 48) Odds ratio (95% CI) 0.98 (0.65 – 1.47) 0.98 Pts receiving post-study anti-EGFR tx – n (%) Arm 1 Arm 2 WT KRAS 42 (12.9) 84 (25.4) MT KRAS 15 (6.8) 36 (16.4) Sensitivity analysis of OS using Branson-Whitehead approachc (pmab + FOLFOX: FOLFOX) WT KRAS 0.74 (0.61 – 0.90) 0.003 MT KRAS 1.06 (0.85 – 1.32) 0.6 a Descriptive. b Restricted to pts with baseline measurable disease per modified RECIST. c Stat Med 2002.