Abstract 3425
Background
Genetic variants of dihydropyrimidine dehydrogenase (DPYD) gene can result in varied enzymatic activity and potential toxicity when receiving 5-FU chemotherapy including treatment related death in up to 1% patients. Current international guidelines suggest an international rate of 3-5% albeit routine prospective pharmacogenomic testing is not currently recommended. However, in a genetically homogenous population such as Ireland, DPYD variant enrichment may support routine testing.
Methods
All patients receiving 5-FU based chemotherapy in South & South-West region of Ireland were prospectively tested from 01/09/2018 to present. The Viapath DPYD genotyping panel which interrogates for 5 variants was used. Toxicity type and grade for all patients were recorded (CTCAE v5.0).
Results
To date, 139 patients have been tested,50.4% male and 49.6% female, median age 63 years. The majority(59%) were being treated for colorectal cancer. Sixteen patients were found to be heterozygous carriers of a DYPD variant with one compound heterozygous variant identified i.e. an overall prevalence of 12 %. No homozygous carriers were identified. Grade ≥3 was observed in 33% DPYD variant carriers compared to 19% in DPYD wild type patients i.e. relative risk of grade ≥3 toxicity is 1.7, p = 0.17.Table:
648P
DPYD Variants | Prevalence % n = 139 | % Rate of ≥ G3 toxicity |
---|---|---|
7(5.0%) | 42% | |
c. 2846A>T | 1(0.7%) | n/a* |
c. 1905 + 1G>A | 3(2.2%) | 100% |
c. 1679T>G | 0 (0%) | n/a* |
c. 1601GA | 5 (3.6%) | 0% |
c. 1905 + 1G>A+c;1236G>A/Hapb3 compound heterozygous | 1(0.7%) | n/a* |
TOTAL:17 (12.2%) |
Conclusions
The study shows a higher than expected prevalence of DPYD variants of 12.2% compared to internationally reported 3-5%. Patients with DPYD variants c.1236G>A and c.1905+1G>A were particularly likely to develop Grade ≥ 3 toxicity. Prospective testing continues to assess the clinical relevance of individual variants in our population.
Legal entity responsible for the study: The authors.
Clinical trial identification
Editorial acknowledgement
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5345 - Short-term Clinical Outcomes of Robotic-Assisted Total Mesorectal Excision in Rectal Cancer after concurrent chemoradiotherapy
Presenter: Pojung Chen
Session: Poster Display session 2
Resources:
Abstract
5489 - Local immune status in cancer cell nests can be a predictor of survival for rectal cancer with neoadjuvant radiotherapy
Presenter: xijin lin
Session: Poster Display session 2
Resources:
Abstract
1653 - Impact of concomitant medications on disease free survival (DFS) and overall survival (OS) in patients from the PETACC8 study.
Presenter: Clémence Brun
Session: Poster Display session 2
Resources:
Abstract
5206 - Updated results of NORDIC 8, a randomised trial of cetuximab every 2 weeks with FOLFIRI or cetuximab with alternating FOLFIRI/FOLFOX in patients with RAS and BRAF wild type metastatic colorectal cancer.
Presenter: Per Pfeiffer
Session: Poster Display session 2
Resources:
Abstract
2992 - Clinical impact of mucinous and poorly differentiated tumors on the outcome of patients with stage II colon cancer: a TOSCA subgroup analysis
Presenter: Gerardo Rosati
Session: Poster Display session 2
Resources:
Abstract
4753 - Exercise improved adjuvant treatment completion rates and treatment-related toxicities in colorectal cancer: A prospective pilot study
Presenter: Hong Jun Kim
Session: Poster Display session 2
Resources:
Abstract
2735 - Bevacizumab plus Oxaliplatin-Based Chemotherapy as Adjuvant Treatment for Colon Cancer (CC): Updated analysis of stage II disease from the AVANT Phase III Randomized trial by the GERCOR Group
Presenter: Aimery De Gramont
Session: Poster Display session 2
Resources:
Abstract
1843 - Multicenter Validation of the Postoperative Carcinoembryonic Antigen Combined Prognostic Model for Stage Ⅲ Colon Cancer
Presenter: Ji Zhu
Session: Poster Display session 2
Resources:
Abstract
2554 - Impact of the IDEA study on clinical practice for stage III colon cancer patients: a French GERCOR - FFCD - GI UNICANCER national survey.
Presenter: Kaissa Ouali
Session: Poster Display session 2
Resources:
Abstract
3285 - Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer
Presenter: Philip Falk
Session: Poster Display session 2
Resources:
Abstract