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 Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
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.