Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy.

Abstract

BACKGROUND:

Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind VEGF receptors 1 and 2 (VEGFR-1 and -2), respectively. This randomized phase II study evaluated the antitumor activity and safety of icrucumab and ramucirumab each in combination with mFOLFOX-6 in patients with metastatic colorectal cancer after disease progression on first-line therapy with a fluoropyrimidine and irinotecan.

PATIENTS AND METHODS:

Eligible patients were randomly assigned to receive mFOLFOX-6 alone (mFOLFOX-6) or in combination with ramucirumab 8 mg/kg IV (RAM+mFOLFOX-6) or icrucumab 15 mg/kg IV (ICR+mFOLFOX-6) every 2 weeks. Randomization was stratified by prior bevacizumab therapy. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, safety, and PK.

RESULTS:

In total, 158 patients were randomized, but only 153 received treatment (49 on mFOLFOX-6, 52 on RAM+mFOLFOX-6, and 52 on ICR+mFOLFOX-6). Median PFS was 18.4 weeks on mFOLFOX-6, 21.4 weeks on RAM+mFOLFOX-6, and 15.9 weeks on ICR+mFOLFOX-6 (RAM+mFOLFOX-6 versus mFOLFOX-6, stratified hazard ratio [HR] 1.116 [95% CI 0.713-1.745], P = 0.623; ICR+mFOLFOX-6 versus mFOLFOX-6, stratified HR 1.603 [95% CI 1.011-2.543], P = 0.044). Median survival was 53.6 weeks on mFOLFOX-6, 41.7 weeks on RAM+mFOLFOX-6, and 42.0 weeks on ICR+mFOLFOX-6. The most frequent adverse events reported on the ramucirumab arm (RAM+mFOLFOX-6) were fatigue, nausea, and peripheral sensory neuropathy; those on the icrucumab arm (ICR+mFOLFOX-6) were fatigue, diarrhea, and peripheral sensory neuropathy. Grade ≥3 serious adverse events occurred at comparable frequency across arms.

CONCLUSIONS:

In this study population, combining ramucirumab or icrucumab with mFOLFOX-6 did not achieve the predetermined improvement in PFS.

CLINICALTRIALSGOV:

NCT01111604.

• Authors: M Moore, S Gill, T Asmis, S Berry, R Burkes, K Zbuk, T Alcindor, A Jeyakumar, T Chan, S Rao, J Spratlin, P A Tang, J Rothenstein, E Chan, J Bendell, F Kudrik, J Kauh, S Tang, L Gao, S R P Kambhampati, F Nasroulah, L Yang, N Ramdas, P Binder, E Strevel
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 27 Issue 12 Pg. 2216-2224 (12 2016) ISSN: 1569-8041 [Electronic] England
• PMID: 27733377 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Irinotecan
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Colorectal Neoplasms (drug therapy, pathology)
• Disease Progression
• Disease-Free Survival
• Drug-Related Side Effects and Adverse Reactions (classification, pathology)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Irinotecan
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neoplasm Metastasis
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Ramucirumab