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

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.

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Prevalence and Predictors of Venous Thromboembolism After Robot-Assisted Radical Cystectomy.

OBJECTIVE: To describe incidence and variables associated with venous thromboembolism (VTE) after robot-assisted radical cystectomy (RARC). METHODS: A retrospective review of the prospectively maintained departmental database was performed. Extended thromboprophylaxis (for 4 weeks postoperatively) was implemented November 2017. Patients were divided into VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) and non-VTE groups. Baseline demographics, disease characteristics and perioperative outcomes were compared. Cochran-Armitage trend test was used to assess trends of VTE. Multivariate logistic regression was used to identify variables associated with VTE. The Kaplan-Meier method was used to depict recurrence free survival (RFS), disease specific survival (DSS), and overall survival (OS). RESULTS: Twenty nine patients (5%) developed VTE (14 developed DVT and 15 developed PE). Median time to DVT was 28 days and to PE was 23 days after RARC. The rate of VTE remained stable between 2005 and 2020 (P= .99). Patients who developed VTE had significantly higher BMI (31 vs 29, P = .04), had COPD more often (34% vs 14%, P < .01) and had longer median hospital stay (8 vs 7 days, P = .01). Multivariate analysis showed that BMI (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.005-1.10; P = .03), COPD (OR 3.24; 95% CI 1.43-7.30; P < .01),and non-organ confined disease (OR 2.73; 95% CI 1.22-6.11; P = 0.01) were associated with VTE. Kaplan-Meier curves showed that patients who developed VTE exhibited similar RFS (79% vs 64%, P = .28), DSS (90% vs 76%, P = .17), and OS (54% vs 52%, P = .76) at 5 years compared to those who did not develop VTE. CONCLUSION: VTE remains a significant complication after RARC. Higher BMI, COPD, and non-organ confined disease were significantly associated with VTE.

Validation of the Khorana Score for Prediction of Venous Thromboembolism After Robot-Assisted Radical Cystectomy.

Introduction: The Khorana score (KS) is used to predict the risk of venous thromboembolism (VTE) for cancer patients. We sought to assess the association between KS and VTE for patients who underwent robot-assisted radical cystectomy (RARC). Materials and Methods: We reviewed our prospectively maintained quality assurance RARC database between 2005 and 2020. KS was calculated for all patients (one point for each body mass index [BMI] ≥35 kg/m2, platelet count ≥350 × 109/L, leukocyte count >11 × 109/L, and hemoglobin level <10 g/dL, or use of erythropoiesis-stimulating agents). All patients received one point by default for the cancer type (bladder). Patients were divided into intermediate-risk (KS 1-2) or high-risk (KS ≥3) groups. Receiver operating characteristic curve was used to assess the ability of KS to predict VTE. Kaplan-Meier curves were stratified based on their KS risk and used to depict overall survival (OS). Multivariate analysis (MVA) was used to identify variables associated with VTE. Results: Out of 589 patients, 33 (6%) developed VTE (18 had deep vein thrombosis and 15 had pulmonary embolism). Five hundred forty-six (93%) patients had intermediate-risk KS and 30 (5%) of them developed VTE. Forty-three (7%) patients were classified as high-risk KS and 3 (7%) developed VTE. This difference was not significant (p = 0.73). The KS area under the curve for VTE prediction was 0.51. On MVA, BMI ≥35 kg/m2 (odds ratio [OR] 2.69, confidence interval [CI] 1.19-6.11, p = 0.02), longer inpatient stay (OR 1.04, CI 1.003-1.07, p = 0.03), and ≥pT3 disease (OR 2.29, CI 1.11-4.71, p = 0.03) were associated with VTE, whereas KS was not associated with VTE (p = 0.68). Five-year OS of patients with intermediate KS was 53% compared with 30% for high-risk KS (log rank p < 0.01). Conclusion: KS underestimated VTE risk after RARC and showed poor accuracy. This highlights the need to develop procedure-specific tools to estimate the risk of VTE after RARC.

NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018.

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected. These NCCN Guidelines Insights explain recent changes in anticoagulants recommended for the treatment of cancer-associated VTE.