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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

4913 - Prospective DPYD testing in colorectal cancer patients in a realworld UK population

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

Topics

Translational Research

Tumour Site

Colon and Rectal Cancer

Presenters

Bryony Eccles

Citation

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

Authors

B.K. Eccles1, A.S. Harle1, S. Pullinger2, C. Holling1, A. Ingram3, S. Stark2, M. Bunce2, G. Melville1, J. Gibbins3, N. Calcutt3, T. Hickish4, M. Flubacher1, T. Marinaki5

Author affiliations

  • 1 Oncology, Poole Hospital NHS Foundation Trust, BH15 2JB - Poole/GB
  • 2 Surgical oncology, Royal Bournemouth Hospital, Bournemouth/GB
  • 3 Oncology, Dorchester County Hospital, Dorchester/GB
  • 4 Oncology, Royal Bournemouth Hospital and University, Bournemouth/GB
  • 5 Purine Research Laboratory, St Thomas Hospital, London/GB
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Resources

Abstract 4913

Background

Polymorphisms within the DPYD gene are present in 7% of Europeans but account for 23% of life-threatening toxicity from fluoropyrimidine (FP) chemotherapy. Four DPYD variants have an adjusted relative risk for toxicity of 1.59 - 4.4. Upfront genotyping is safe and cost effective but not mandated by ESMO guidelines. To reduce the risk of life-threatening toxicity we implemented prospective DPYD testing as standard practice.

Methods

Consecutive colorectal cancer (CRC) patients in a UK cancer centre due to receive FP chemotherapy were genotyped by real time PCR for known clinically relevant DPYD mutations: c.1905+G>A 2*, c.2846A>T, c.1679T>G and c.1605 G>A and from March 2017, c.1236G>A/HapB. We followed published recommendations for dose reduction or alternative drug. Demographics, dose, toxicity and survival data were collected.Table: 560P

DPYD Heterozygote mutations (No homozygote or compound heterozygote mutations)Adjusted RRNo. (%)Mean 1st dose %Any grade 3/4 toxicity No. (%)Grade 3/4 diarrhoea No. (%)
c.1905+G>A1.593 (2%)77%10
c.2846A>T3.022 (1%)100%11
c.1679T>G4.40 (0%)
c.1236G.A/ HapB31.597 (3%)76%10
c.1601G>A1.52 (Non significant)11(5)%80%42
Any heterozygote mutation23 (10%)80%7 (30%)3 (13%)
Wildtype1207 (90%)93%42 (20%)20 (10%)
Total 58% adjuvant 27% neoadjuvant 24% palliative230 (100%)92%49 (21%)23 (10%)

Results

Between 1/1/16-31/12/2017, 230 patients were tested. 72% had capecitabine, 24% 5-fluorouracil, and 4% raltitrexed combinations. After dose reduction or alternative therapy, grade 3/4 diarrhoea was similar in wildtype and mutations (10 vs 13%) and any toxicity admissions were not significantly different (p = 0.284). There were no treatment deaths.

Conclusions

To our knowledge, we are the only UK centre to implement prospective DPYD testing in routine clinical practice for CRC patients. In published data of unselected CRC patients the G3/4 GI toxicity is 15%, but if 2* variant is present this increases to 73%. In the latter population, genotype guided dosing reduces the risk to 28%. Our rate for all variants was 10% but limited by small numbers. Pharmacokinetics in another study showed adequate 5FU exposure with a 50% dose reduction, alleviating underdosing concerns. The growing evidence supports prospective DPYD testing. We have shown it is practical and may mitigate serious toxicities.

Clinical trial identification

Legal entity responsible for the study

Bryony Eccles.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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