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
4250 - Phase II study of avelumab in combination with cetuximab as a rechallenge strategy in pre-treated RAS wild type metastatic colorectal cancer patients: CAVE (cetuximab-avelumab) Colon.
Presenter: Erika Martinelli
Session: Poster Display session 2
Resources:
Abstract
5234 - The ORCHESTRA trial; A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).
Presenter: Lotte Bakkerus
Session: Poster Display session 2
Resources:
Abstract
5294 - EMERGE: Epigenetic Modulation of the Immune Response in Gastrointestinal cancers
Presenter: Elizabeth Cartwright
Session: Poster Display session 2
Resources:
Abstract
913 - Phase III, international, multicenter, randomized, open-label trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) alone for surgically resected pancreatic adenocarcinoma (APACT): subgroup analyses
Presenter: Margaret Tempero
Session: Poster Display session 2
Resources:
Abstract
1668 - FOLFIRINOX in locally advanced (LA) and borderline resectable (BR) pancreatic adenocarcinoma : update of the AGEO cohort.
Presenter: Edouard Auclin
Session: Poster Display session 2
Resources:
Abstract
2559 - Impact of adjuvant treatment with nab-paclitaxel and gemcitabine (nab-P+GEM) vs gemcitabine alone (GEM) on health-related quality of life (QoL) in patients (pts) with surgically resected pancreatic adenocarcinoma (PA) in the Adjuvant Pancreatic Adenocarcinoma Clinical Trial (APACT)
Presenter: Hanno Riess
Session: Poster Display session 2
Resources:
Abstract
4897 - Early detection of pancreatic ductal adenocarcinoma using methylation signatures in circulating tumor DNA
Presenter: Xiao-ding Liu
Session: Poster Display session 2
Resources:
Abstract
1755 - Evaluation of minimal important difference (MID) for the European Organisation for Research and Treatment of Cancer (EORTC) Pancreatic Cancer Module (PAN26) in patients with surgically resected pancreatic adenocarcinoma
Presenter: Michele Reni
Session: Poster Display session 2
Resources:
Abstract
2876 - Multispectral analysis of lymphocyte complexity in periampullary adenocarcinoma
Presenter: Sebastian Lundgren
Session: Poster Display session 2
Resources:
Abstract
1902 - Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)
Presenter: Jae Ho Jeong
Session: Poster Display session 2
Resources:
Abstract