551P - RAS analysis of the PLANET study: Phase II trial of panitumumab (P) plus FOLFOX4 or FOLFIRI in subjects with wild-type (WT) KRAS colorectal cancer...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cytotoxic agents
Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological therapy
Presenter Albert Abad
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors A. Abad1, B. Massuti Sureda2, C. Grávalos3, P. Escudero4, C. Guillen-Ponce5, A. Gómez6, M.J. Safont7, J. Gallego Plazas8, J. Sastre9, C. Pericay10, R. Dueñas11, C. López12, F. Losa13, M. Valladares-Ayerbes14, E. González Flores15, L. Robles Díaz3, L. Layos1, A. Carrato16, E. Aranda17
  • 1Medical Oncology, ICO. Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 2Medical Oncology, Hospital General Universitario de Alicante, ES-03010 - Alicante/ES
  • 3Medical Oncology, Hospital Universitario Doce de Octubre, Madrid/ES
  • 4Medical Oncology, Hospital Universitario Lozano Blesa, Zaragoza/ES
  • 5Medical Oncology Department, Hospital Ramón y Cajal, 28034 - Madrid/ES
  • 6Medical Oncology, Hospital Reina Sofía, Córdoba/ES
  • 7Medical Oncology, Hospital General de Valencia, Valencia/ES
  • 8Medical Oncology, Hospital Universitario de Elche, 03202 - Elche/ES
  • 9Medical Oncology, Hospital Universitario Clínico San Carlos, 28040 - Madrid/ES
  • 10Medical Oncology, Corporació Sanitària Parc Taulí Institut Universitari, 08208 - Sabadell/ES
  • 11Medical Oncology, Complejo Hospitalario de Jaén, Jaén/ES
  • 12Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander/ES
  • 13Medical Oncology, Hospital General de L´Hospitalet, 08906 - Barcelona/ES
  • 14Medical Oncology, Hospital Universitario a Coruña - a Coruña, ES-15006 - La Coruña/ES
  • 15Medical Oncology Department, Hospital Universitario Virgen de las Nieves, 18011 - Granada/ES
  • 16Medical Oncology, Hospital Ramon y Cajal, ES-28034 - Madrid/ES
  • 17Oncology Department, IMIBIC-Hospital Reina Sofía, Córdoba/ES

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-FOLFIRI Total
WT RAS, n 27 26 53
ORR (not confirmed) 77.8 (62.1–93.5) 73.1 (56.0–90.1) 75.5 (63.9–87.1)
PFS, mo 12.8 (6.2–22.0) 14.8 (7.1–18.7) 0.675 13.4 (9.9–18.6)
OS, mo 39.0 (26.4–NA) 45.8 (32.8–51.5) 0.634 44.7 (32.8–51.5)
Mutant RAS, n 4 7 11
ORR (not confirmed) 50 (1.0–99.0) 57.1 (20.5–93.8) 54.6 (25.1–84.0)
PFS, mo 15.4 (3.7–24.9) 12.6 (1.9–16.2) 0.699 12.6 (3.7–24.9)
OS, mo 31.4 (20.6–NA) 42.4 (13.7–42.4) 0.391 31.4 (13.7–NA)
P value* WT vs Mutant RAS
PFS 1.000 0.238 0.403
OS 0.843 0.616 0.724

*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.