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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

2869 - Patient selection for targeting integrin with abituzumab in patients with metastatic colorectal cancer (mCRC). A retrospective analysis of the randomized phase I/II Poseidon study.

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Rita Laeufle

Citation

Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281

Authors

R. Laeufle1, D. Arnold2, S. Kopetz3, J. Straub4, R. Bruns5, G. Massimini6, R. Debenedetto7, R. Linke7, E. Elez Fernandez8, J. Tabernero9

Author affiliations

  • 1 Clinical Development And Medical Affairs, SFJ Pharmaceuticals, 94588 - Pleasanton/US
  • 2 2. Med. Abteilung, Asklepios Klinik Altona, 22763 - Hamburg/DE
  • 3 Department Of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 4 Global Early Development, Merck KGaA, 64293 - Darmstadt/DE
  • 5 Biostatistics, Merck KGaA, 64293 - Darmstadt/DE
  • 6 Global Research And Development, Merck KGaA, 64293 - Darmstadt/DE
  • 7 Clinical Development And Medical Affairs, SFJ-Pharmaceuticals, 94588 - Pleasanton/US
  • 8 Gastrointestinal Cancer And Drug Development, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 9 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
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Resources

Abstract 2869

Background

Adding abituzumab (EMD 525797) a humanized monoclonal IgG2 antibody, targeting αν integrin subunit to the control arm (irinotecan+cetuximab) failed to demonstrate a statistically significant PFS benefit in a phase I/II in second line KRAS wild-type (KRAS wt exon-2) mCRC. A pre-planned explorative biomarker analysis suggested that high integrin ανβ6 expression may be negatively prognostic for OS in the control arm and predictive for prolonged OS with abituzumab treatment. {Elez et al Annals of Oncology, Volume 26, Issue 1, 1 January 2015, Pages 132–140}.

Methods

Further retrospective analysis of Poseidon study data were performed (n = 98 patients with high and n = 99 low ανβ6 expression) to correlate the impact of location of tumor (left n = 152 versus right n = 44, and one patient had both right and left colorectal cancer) and integrin ανβ6 expression (low versus high) on overall survival (OS), progression free survival (PFS) and objective response rate (ORR) of abituzumab added to irinotecan+cetuximab.

Results

This retrospective explorative analysis suggest that patients with left sided KRAS wt mCRC and high expression of ανβ6 showed the most benefit for median OS of 25.6 months versus 10.2 months (HR 0.36 [95% CI 0.17; 0.75]; median PFS of 8.6 months versus 4.2 months (HR 0.61 [95% CI 0.31; 1.22]); ORR. 9/20 (45.0%) versus 5/22 (22.7%), when treated with abituzumab 1000 mg + irinotecan+cetuximab versus irinotecan+cetuximab alone. No treatment benefit was observed in right sided mCRC with high expression of ανβ6 and in all mCRC with low expression of ανβ6.

Conclusions

Although the sample size is small, patients with left sided KRAS wt mCRC and high expression of ανβ6 integrin in their tumor seem to benefit most from the addition of abituzumab to irinotecan+cetuximab compared to irinotecan+cetuximab alone. A prospective study in 1L left sided RAS wild-type mCRC with high expression of ανβ6 is planned with the addition of abituzumab 1000mg to SOC.

Clinical trial identification

Explorative, retrospective data analysis of study NCT01008475; first release October 19, 2009.

Legal entity responsible for the study

Merck KGaA and SFJ Pharmaceuticals.

Funding

Merck KGaA and SFJ Pharmaceuticals.

Editorial Acknowledgement

Disclosure

R. Laeufle: Consultant: SFJ Pharmaceuticals. D. Arnold: Consultancy, honoraria: Roche, Merck Serono; Research funding to the Principal Investigator: Roche, Sanofi Aventis. S. Kopetz: Intellectual property rights: Amgen, Array, Bayer, Genentech, Taiho; Ownership interest: MolecularMatch. J. Straub, R. Bruns, G. Massimini: Employee: Merck KGaA. R. Debenedetto: CEO: SFJ Pharmaceuticals. R. Linke: CMO: SFJ Pharmaceuticals. J. Tabernero: Consulting or advisory role: Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai Pharma, Lilly, Merck Serono, MSD, Novartis, Pfizer, Roche, Sanofi, Symphony Evolution, Taiho Pharmaceutical, Takeda. All other authors have declared no conflicts of interest.

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