Potential association of SULT2A1 and ABCG2 variant alleles with increased risk for palbociclib toxicity

Abstract

Aim: This study evaluated associations between CYP3A4*22 and variants in other pharmacogenes (CYP3A5, SULT2A1, ABCB1, ABCG2, ERCC1) and the risk for palbociclib-associated toxicities.Materials & methods: Two hundred cancer patients who received standard-of-care palbociclib were genotyped and associations with toxicity were evaluated retrospectively.Results: No significant associations were found for CYP3A4*22, CYP3A5*3, ABCB1_rs1045642, ABCG2_rs2231142, ERCC1_rs3212986 and ERCC1_rs11615. Homozygous variant carriers of SULT2A1_rs182420 had higher incidence of dose modifications due to palbociclib toxicity (odds ratio [OR]: 4.334, 95% CI: 1.057-17.767, p = 0.042). ABCG2_rs2231137 variant carriers had borderline higher incidence of grade 3-4 neutropenia (OR: 4.14, 95% CI: 0.99-17.37, p = 0.052).Conclusion: Once validated, SULT2A1 and ABCG2 variants may be useful to individualize palbociclib dosing to minimize toxicities and improve treatment outcomes.

Keywords: Breast cancer; CDK4/6 inhibitors; palbociclib; pharmacogenetics; toxicity.

Figure 1.

Multivariable associations between pharmacogenetic variants and palbociclib toxicity. SULT2A1_rs182420 homozygous (C/C) variant patients were at increased risk for toxicity-related treatment modifications (OR: 4.33, 95% CI: 1.06–17.77, p = 0.042). Albeit not statistically significant, ABCG2_rs2231137 heterozygous (C/T) variant carriers were more likely to develop grade 3–4 neutropenia (OR: 4.14, 95% CI: 0.99–17.37, p = 0.052). CI: Confidence interval; Tx: Treatment.