551PRAS ANALYSIS OF THE PLANET STUDY: PHASE II TRIAL OF PANITUMUMAB (P) PLUS FOLFOX4 OR FOLFIRI IN SUBJECTS WITH WILD-TYPE (WT) KRAS COLORECTAL CANCER (CRC) AND LIVER-LIMITED DISEASE (LLD)

Abstract Aim: Patients (pts) with RAS mutations other than KRAS exon 2 do not benefit from P. We explored the effect of these mutations in the efficacy of P-FOLFOX4 or P-FOLFIRI, as 1st-line treatment in WT KRAS CRC pts with LLD. Methods: Phase II, open-label, multicentre study in which WT KRAS CRC pts ≥ 18 years (y) with ≥4 liver metastases; at least 1 >10 cm; or not resectable were randomized to P-FOLFOX4 or P-FOLFIRI. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analysed according to RAS status (exons 2, 3, 4 of KRAS/NRAS). Results: 77 pts were analysed (38 P-FOLFOX4 [82% male, median age: 65 y]/ 39 P-FOLFIRI [72% male, 63 y]). It was possible to determine RAS status in 83.1% of pts (82.8% WT, 17.2% mutant). Higher ORR and longer PFS and OS were observed in WT-RAS versus mutant RAS subgroups in both P-FOLFOX4 and P-FOLFIRI groups, although differences were not significant, probably due to small sample sizes (Table). There were no significant differences between P-FOLFOX4 and P-FOLFIRI within each of the RAS strata, either. Peri-operative and overall safety were similar, except for higher grade 3/4 neutropenia (39.5% vs 10.3%; p = 0.003) and neuropathy (13.2% vs 0%;p = 0.025) in the P-FOLFOX4 arm.P-FOLFOX4 % or median (95% CI)P-FOLFIRI % or median (95% CI)P value* P-FOLFOX4 vs P-FOLFIRITotalWT RAS, n272653ORR (not confirmed)77.8 (62.1–93.5)73.1 (56.0–90.1)75.5 (63.9–87.1)PFS, mo12.8 (6.2–22.0)14.8 (7.1–18.7)0.67513.4 (9.9–18.6)OS, mo39.0 (26.4–NA)45.8 (32.8–51.5)0.63444.7 (32.8–51.5)Mutant RAS, n4711ORR (not confirmed)50 (1.0–99.0)57.1 (20.5–93.8)54.6 (25.1–84.0)PFS, mo15.4 (3.7–24.9)12.6 (1.9–16.2)0.69912.6 (3.7–24.9)OS, mo31.4 (20.6–NA)42.4 (13.7–42.4)0.39131.4 (13.7–NA)P value* WT vs Mutant RASPFS1.0000.2380.403OS0.8430.6160.724*Wilcoxon test; NA = not achieved; CI = confidence interval; mo = months. Conclusions: In pts with WT KRAS CRC and LLD, P plus chemotherapy provide a high response rate, allowing potentially curative resection. Better outcomes are observed in the WT RAS subgroup, without differences between the two regimens. Supported by Amgen S.A. Disclosure: B. Massuti Sureda: Consultant or advisory role: Amgen Honoraria. Amgen; M. Valladares-Ayerbes: Consultant or advisory role: Merck, Amgen Honoraria: Merck, Amgen Research funding: Merck, Amgen E. Aranda: Advisory Role: Roche, Merck. All other authors have declared no conflicts of interest.