Table 5.

Unadjusted relative risk of severe fluoropyrimidine‐related adverse events

DPYD variant	Genotype‐guided dosing current cohort a RR (95% CI) d	Patients treated without genotype‐guided dosing b RR (95% CI) d	Genotype‐guided dosing literature cohort c RR (95% CI) d
c.1905+1G>A	1.08 (0.43–2.74)	2.87 (2.14–3.86)	1.31 (0.63–2.72)
c.2846A>T	0.85 (0.40–1.82)	3.11 (2.25–4.28)	2.00 (1.19–3.34)
c.1679T>G	NA e	4.30 (2.10–8.80)	NA e
c.1236G>A	0.54 (0.19–1.52)	1.72 (1.22–2.42)	1.69 (1.18–2.42)

Abbreviations: CI, confidence interval; NA, not applicable; RR, relative risk.

^a Our genotype‐guided cohort: 50% dose reduction recommended for carriers of c.1905+1G>A, c.2846A>T, and c.1679T>G; 25% −50% dose reduction for carriers of c.1236G>A.

^b Meulendijks et al. historical cohort derived from a meta‐analysis ¹¹ : standard of care dosing with adjustment due to tolerability resulting in the assumption that given no genotype was known the dose intensity was equivalent between DPYD variant carriers and noncarriers.

^c Henricks et al. genotype guided cohort ¹⁶ : 50% dose reduction recommended for carriers of c.1905+1G>A or c.1679T>G; 25% dose reduction for carriers of c.2856A>T or c.1236G>A. Followed by dose escalation pending patient tolerance.

^d Unadjusted RRs with 95% CIs are discussed due to small sample size of variant carriers in genotype‐guided cohorts. Risks are calculated compared with noncarriers of the individual variant of interest.

^e Only one c.1679T>G carrier was detected in each genotype‐guided cohort. In both cohorts, the carrier was treated with 50% dose reduction and did not suffer a fluoropyrimidine‐related adverse event.