O-0008 - Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone, as second-line treatment for patients with KRAS wild-type...

Date 27 June 2014
Event World GI 2014
Session Presentation of selected abstracts
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter E. Elez
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors E. Elez1, I. Kocáková2, T. Höhler3, U. Martens4, C. Bokemeyer5, B. Melichar6, M. Smakal7, T. Cso˝szi8, D. Vyushkov9, E. Topuzov10, R. Orlova11, S. Tjulandin12, F. Rivera13, J. Straub14, R. Bruns14, S. Quaratino14
  • 1Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona/ES
  • 2Klinika Komplexní Onkologické Péče, Masarykuv Onkologicky Ustav, Brno/CZ
  • 3Medizinische Klinik I, Prosper-Hospital, Recklinghausen/DE
  • 4Dept. of Hematology/Oncology, Cancer Center Heilbronn-Franken, Heilbronn/DE
  • 5Dept. Of Oncology/hematology, University Hospital Hamburg, Hamburg-Eppendorf/DE
  • 6Fakultni Nemocnice Olomouc, Olomouc/CZ
  • 7Onkologicke Oddeleni, Horovice/CZ
  • 8Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rend. Int., Szolnok/HU
  • 9State Healthcare Institution of Omsk Regional Oncology Dispensary, Omsk/RU
  • 10GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen of Healthcare, St Peterburg/RU
  • 11City Clinical Oncology Dispensary, Saint-Peterburg/RU
  • 12S.I. Russian Oncological Research Center n.a. N.N. Blokhin, Moscow/RU
  • 13HU Marques de Valdecilla, Santander/ES
  • 14Merck KGaA, Darmstadt/DE



Integrins can play a direct role in tumor progression and metastasis, and have been found to be highly expressed on tumor cells in colorectal cancer (CRC). Abituzumab (EMD 525797, DI17E6) is a humanized monoclonal IgG2 antibody that specifically targets the α&ngr; subunit of human integrin receptors. In preclinical models, abituzumab demonstrated antitumor activity, which was enhanced when combined with cetuximab. POSEIDON is a Phase I/II open-label, randomized, controlled, multicenter trial (NCT01008475) to investigate the safety and efficacy of abituzumab combined with standard of care (SoC; cetuximab plus irinotecan) versus SoC alone. In the safety run-in (Phase I part), no dose-limiting toxicities were observed for abituzumab up to 1,000 mg biweekly plus SoC (Elez et al. J Clin Oncol 2012;30[15_Suppl]:3539). Herein, the results of the Phase II part are reported.


Patients were randomized 1:1:1 to receive either abituzumab 500 mg (Arm A) or 1,000 mg (Arm B) i.v. every 2 weeks per 2-week cycle, in combination with SoC (cetuximab [400 mg/m2, day 1 cycle 1; then 250 mg/m2 weekly] plus irinotecan [180 mg/m2 every 2 weeks]), or SoC alone (Arm C). The primary endpoint was progression-free survival (PFS) as assessed by the investigator in the intention-to-treat population. Secondary objectives included the assessment of overall survival (OS), safety and tolerability; further objectives were the evaluation of potential prognostic and predictive biomarkers for PFS and OS. Eligible patients had confirmed KRAS wild-type CRC with documented distant metastasis, failure after prior oxaliplatin/fluoropyrimidine-containing treatment, ≥1 radiographically documented measurable lesions according to RECIST (version 1.0), and ECOG performance status 0–1.


In total, 216 patients were randomized between 2009–2013: 73 patients to Arm A, 71 to Arm B, and 72 to Arm C; baseline characteristics were balanced. Median PFS per investigator assessment was 5.4 months in Arm A (HR, 1.13 [95% CI, 0.78, 1.64]) and 5.6 months in Arm B (HR, 1.11 [95% CI, 0.77, 1.61]), vs 5.6 months in Arm C. A trend towards improved median OS was observed in Arms A and B, vs Arm C (15.0 and 14.4, vs 11.6 months, respectively). There was no difference in response rates (RRs) between the 3 treatment arms (27.4%, 25.4%, and 26.4% for Arms A, B, and C, respectively). Grade ≥3 treatment-emergent adverse events (TEAEs) were observed in 72%, 78%, and 67% of patients in Arms A, B, and C, respectively, and 13%, 10%, and 8% of patients experienced TEAEs with fatal outcome (none considered as related to abituzumab). High integrin αvß6 expression was observed in 98/197 analyzed tumor tissue samples; high expression was associated with longer OS (HR, 0.48 [95% CI, 0.28, 0.82]) and better RR (31% vs 16%) for abituzumab-treated patients vs SoC.


The primary endpoint of increased PFS in the study was not met, though a trend towards improved OS was observed. In the subgroup of patients with tumors characterized by high expression of αvß6, abituzumab prolonged OS and doubled the RR. The overall safety profile of abituzumab in combination with SoC was acceptable.