Predictive value of clinical toxicities of chemotherapy with fluoropyrimidines and oxaliplatin in colorectal cancer by DPYD and GSTP1 gene polymorphisms

Abstract Background Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to chemotherapy-related adverse events. In the present study, we purposed to assess the impact of DPYD and GSTP1 variants on the toxicity of adjuvant chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment. Methods Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drug-based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A, and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed. Results The data suggest that the incidence of DPYD*5A, DPYD*9A, and GSTP1 c.313A>G variants were 38.4%, 24%, and 32.7%, respectively. DPYD*2A variant was not found. A total of 23 patients (22.1%) suffered severe vomiting and 19 patients (18.3%) suffered severe anemia. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe vomiting and skin ulceration (p = 0.042 and p = 0.018, respectively). Patients with GSTP1 c. 313A>G mutant type contributed to a higher risk for grade severe toxicity compared with wild genotype (p = 0.027). Nevertheless, no significant difference was found between patients with DPYD*2A, *5A, and *9A for chemotherapeutic toxicity. Conclusions The results demonstrated that GSTP1 polymorphisms were useful predictors of severe events. Screening of single-nucleotide polymorphisms of GSTP1 in colorectal cancer patients before chemotherapy may help to realize personalized therapy.

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Predictive value of clinical toxicities of chemotherapy with fluoropyrimidines and oxaliplatin in colorectal cancer by DPYD and GSTP1 gene polymorphisms

10.21203/rs.3.rs-73108/v3 ◽

2020 ◽

Author(s):

Xunwei Deng ◽

Jingyuan Hou ◽

Qiaoting Deng ◽

Zhixiong Zhong

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Direct Sequencing ◽

Dihydropyrimidine Dehydrogenase ◽

Severe Toxicity ◽

Nucleotide Polymorphisms ◽

Mutant Type ◽

Severe Vomiting ◽

Significant Difference ◽

The Impact

Abstract Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. In the present study, we purposed to assess the impact of DPYD and GSTP1 variants on the toxicity of adjuvant chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment.Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A, and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed.Results: The data suggest that the incidence of DPYD*5A, DPYD*9A, and GSTP1 c.313A>G variants were 38.4%, 24%, and 32.7%, respectively. DPYD*2A variant was not found. A total of 23 patients (22.1%) suffered severe vomiting and 19 patients (18.3%) suffered severe anemia. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe vomiting and skin ulceration (p = 0.042 and p = 0.018, respectively). Patients with GSTP1 c. 313A>G mutant type contributed to a higher risk for grade severe toxicity compared with wild genotype (p = 0.027). Nevertheless, no significant difference was found between patients with DPYD*2A, *5A, *9A for chemotherapeutic toxicity.Conclusions: The results demonstrated that GSTP1 polymorphisms were useful predictors of severe events. Screening of single nucleotide polymorphisms of GSTP1 in colorectal cancer patients before chemotherapy may help to realize personalized therapy.

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Predictive value of clinical toxicities of chemotherapy with fluoropyrimidines and oxaliplatin in colorectal cancer by DPYD and GSTP1 gene polymorphisms

10.21203/rs.3.rs-73108/v2 ◽

2020 ◽

Author(s):

Xunwei Deng ◽

Jingyuan Hou ◽

Qiaoting Deng ◽

Zhixiong Zhong

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Direct Sequencing ◽

Dihydropyrimidine Dehydrogenase ◽

Severe Neutropenia ◽

Severe Toxicity ◽

Nucleotide Polymorphisms ◽

Significant Difference ◽

Colorectal Cancer Patients ◽

The Impact

Abstract Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. In the present study, we purposed to assess the impact of DPYD and GSTP1 variants on toxicity of chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment.Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A, and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed. Results: The data suggest that the incidence of DPYD*5A, DPYD*9A, and GSTP1 c.313A>G variants were 37.5%, 24%, and 31.7%, respectively. DPYD*2A variant was not found. A total of 38 patients (36.5%) suffered severe neutropenia and 23 patients (22.1%) suffered severe vomiting. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe neutropenia and ulceration (p = 0.010 and p = 0.034, respectively). Patients with GSTP1 c. 313A>G wild type contributed to a higher risk for grade severe toxicity compared with A/G + G/G genotype (p = 0.024). Nevertheless, no significant difference was found between patients with DPYD*9A T/T and T/C + C/C genotype for chemotherapeutic toxicity.Conclusions: The results demonstrated that DPYD*5A and GSTP1 polymorphisms were useful predictors of severe events. Screening of single nucleotide polymorphisms of DPYD and GSTP1 in colorectal cancer patients prior to chemotherapy may help to realize personalized therapy.

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Predictive Value of Clinical Toxicities to Chemotherapy with Fluoropyrimidines and Oxaliplatin in Colorectal Cancer by DPYD and GSTP1 Genes Polymorphisms

10.21203/rs.3.rs-73108/v1 ◽

2020 ◽

Author(s):

Xunwei Deng ◽

Jingyuan Hou ◽

Qiaoting Deng ◽

Zhixiong Zhong

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Direct Sequencing ◽

Dihydropyrimidine Dehydrogenase ◽

Severe Neutropenia ◽

Severe Toxicity ◽

Nucleotide Polymorphisms ◽

Significant Difference ◽

Grade 3 ◽

Colorectal Cancer Patients

Abstract Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. The present study was aimed to determine the role of DPYD and GSTP1 variants on patient chemotherapy toxicity risk among the Hakka population, minimize adverse events and in order to maximize therapy outcome for individualized treatment.Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed. Results: The data suggest that the incidence of DPYD*5A, DPYD*9A and GSTP1 c.313A>G variants were 37.5%, 24% and 31.7%, respectively. DPYD*2A variant was not found. A total of 38 patients (36.5%) suffered severe neutropenia and 23 patients (22.1%) suffered severe vomiting. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe neutropenia and ulceration (p = 0.010 and p = 0.034, respectively). Patients with GSTP1 c.313A>G wild type contributed to higher risk for grade severe toxicity compared with A/G + G/G genotype (p = 0.024). However, there was no significant difference between patients with DPYD*9A T/T and T/C + C/C genotype for chemotherapeutic toxicity.Conclusions: The results demonstrated that DPYD*5A and GSTP1 polymorphisms were useful predictors for severe events. Screening of single nucleotide polymorphisms of DPYD and GSTP1 in colorectal cancer patients prior to chemotherapy may help to realize personalized therapy.

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Incidence and significance of K-RAS mutation in first line treatment of colorectal cancer (cc): Experience of a single institution (Hospital Universitario Central de Asturias (HUCA))

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15081 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15081-e15081

Author(s):

J. Vieitez ◽

P. Jiménez Fonseca ◽

M. Fernandez de Sanmamed ◽

A. S. Pitiot ◽

G. Crespo ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Data ◽

Direct Sequencing ◽

Stage Iv ◽

Sequencing Data ◽

First Line ◽

Ras Gene ◽

Mutant Type ◽

Ras Mutation ◽

Significant Difference

e15081 Background: Although the significance of K-RAS mutation and cetuximab/panitumumab has been established in first line (ASCO 08 abstract 2# and 4000#) and in previously treated patients (pts) (NEJM 2008; 359: 1757. JCO 2008; 26: 374. JCO 2008; 26: 1626), data of the significance of this mutation in relation to bevacizumab is scarcer (JNCI 2005; 97: 981). Methods: Sample tissue of alive patients diagnosed of stage IV colorectal cancer were analyzed for the presence of K-RAS mutation by PCR amplification and direct sequencing. Data regarding presence of K-RAS mutation were retrospectively analyzed in relation to clinical data. Results: From IV to XII 08 122 paraffin embedded samples were analyzed. The percentage of mutant cases were 41% (95% CI 32–51%). The most frequent mutant type was Gly12Asp (37%) followed by Gly12Val (25%) and Gly13Asp (19%). We have clinical data of 94 pts. 62 were men and 32 female. 25 pts had received previous complementary treatment; in 80 pts primary tumor was previously resected (85%); median number of affected organs was 1 (1–4); in first line 76 pts received bevacizumab and 18 did not received any biological agent. Response Rate (RR) between mutant and no mutant pts was 48% (95% CI 37–59%) vs 47.8% (95% CI 32–63%) (p=0.92). Median follow up was 15.4 months. Progression free survival was 15 months for mutant and native K-RAS. There were no differences in response or PFS in any subgroup studied. Multivariable Cox analysis did not find any significant difference between sex (p=0.78), primary resected organ (p=0.28), liver metastases (p=0.37), LDH value at diagnosis (p=0.0.43), employ of biological agents in first line (p=0.37) or mutation in K-RAS gene (p=0.68). Conclusions: The percentage of K-RAS mutants is coherent with the results of the literature; mutations Gly12Asp, Gly12Val, and Gly13Asp represents the majority of the cases (81%); no significant relation was found between responses or DFS and mutations in the gene. No significant financial relationships to disclose.

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The Clinical Significance of Promoter Methylation of Fluoropyrimidine Metabolizing and Cyclooxygenase Genes in Colorectal Cancer

Epigenetics Insights ◽

10.1177/2516865720986231 ◽

2021 ◽

Vol 14 ◽

pp. 251686572098623

Author(s):

Mariam Ahmed Fouad ◽

Salem Eid Salem ◽

Marwa M. Hussien ◽

Doaa Mohamed Badr ◽

Abdelrahman N. Zekri ◽

...

Keyword(s):

Colorectal Cancer ◽

Promoter Methylation ◽

Dihydropyrimidine Dehydrogenase ◽

Methylation Status ◽

Pairwise Comparisons ◽

Specific Pcr ◽

Significant Difference ◽

High Level ◽

The Impact ◽

Cox2 Expression

Aims: This study investigated the impact of promoter methylation of flouropyrimidine (FP) metabolizing and cyclooxygenase 2 (COX2) genes on their mRNA expression and on the clinical outcome of colorectal cancer (CRC) patients. Methods: Methylation specific-PCR and real time-PCR of thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and COX2 were performed at baseline and after 3 and 6 months of FP therapy. Pairwise comparisons were conducted between the subgroups of CRC patients. The event free survival (EFS) and the hazard of progression were estimated by univariate and multivariate analyses. Results: At baseline CRC patients, both TS and TP were overexpressed, in spite of the unmethylation of TS and the full methylation of TP genes. Significant downexpression of DPD and COX2 were associated their promoter’s methylation. At the end of FP therapy, TS, DPD and COX2 were overexpressed by 7.52, 2.88 and 3.45 folds, respectively, while TP was downexpressed by 0.54 fold. However, no change was observed in the methylation status of genes with FP therapy. Pairwise comparisons revealed significant difference in the expression and the methylation status of genes according to the clinicopathological characters of CRC patients either at baseline or after FP therapy. The overexpression of DPD and COX2 genes were indicators for a poor EFS of CRC patients. Also, the high level of COX2 expression was found to be significantly correlated with the hazard of progression (HR = 1.73, 95% CI = 1.02-3.03). Conclusion: The promoter methylation of FP metabolizing and COX2 genes has significant impact on the expression and the treatment outcome of CRC patients.

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Prospective cohort study of the impact of hospital-wide dihydropyrimidine dehydrogenase (DPYD) genotype testing for fluoropyrimidine-based chemotherapy on adverse events and hospital costs.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3028 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3028-3028

Author(s):

Theodore John Wigle ◽

Brandi Povitz ◽

Wendy Teft ◽

Robin Legan ◽

John Gordon Lenehan ◽

...

Keyword(s):

Adverse Events ◽

Health Care Providers ◽

Prospective Cohort ◽

Primary Outcome ◽

Dihydropyrimidine Dehydrogenase ◽

Care Providers ◽

Wild Type ◽

Significant Difference ◽

Grade 3 ◽

The Impact

3028 Background: Fluoropyrimidines remain integral components of modern chemotherapy for solid tumors, and their toxicities can be reduced by pretreatment DPYD genotyping. Our main objective was to demonstrate the feasibility of implementing a hospital-wide pretreatment DPYD testing service based on the CPIC 2013 guideline on fluoropyrimidines and DPYD. Methods: We enrolled participants prior to planned fluoropyrimidine treatment as well as those who had experienced adverse events (AEs) after initiation of therapy, from December 1, 2013 to November 30, 2018. The patients tested pretreatment were analyzed as a prospective cohort to assess AEs within 90 days of fluoropyrimidine initiation and associated hospital cost. The primary outcome was the rate of severe global fluoropyrimidine-related toxicity in the pretreatment cohort (grade≥3, CTCAE v.4.0.3). Results: Of 1362 patients genotyped for DPYD within the study period 1041 were enrolled pretreatment and included in the primary analysis. The median age was 65 years (19-90), 57% male, 51% 5-FU, and 49% capecitabine. Dose reductions were recommended for 21 DPYD variant carriers who were detected pretreatment. There was no significant difference in the primary outcome between DPYD variant (29%) and wild type (18%) patients (Fisher’s exact test p = 0.25). Costs associated with ER visits and hospitalizations at our tertiary care centre were $1,268 (89-8,562) (Median (IQR)) and $2,961 (341-13,567) for DPYD variant (n = 4) and wild-type (n = 99) patients respectively. Post-AE genotyping (n = 70) found five DPYD variant patients; all experienced grade≥3 toxicity, costs were $15,825 (10,962-25,310), and one poor metabolizer died due to complications. Targeted next generation exome sequencing of DPYD wild-type patients who experienced severe AEs identified five potentially deleterious genetic variants in ABC efflux transporters. Conclusions: Pretreatment DPYD genotype guided dosing of fluorouracil and capecitabine is feasible and benefits patients, health care providers, and hospitals. Our data supports adoption of pretreatment DPYD genotyping as a standard of care.

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Impact of cytochrome P450 2C19 polymorphisms on the clinical efficacy and safety of voriconazole: an update systematic review and meta-analysis

10.22541/au.162546769.92188192/v1 ◽

2021 ◽

Author(s):

Ying Zhang ◽

Xu Hao ◽

Kelu Hou ◽

Lei Hu ◽

Jingyuan Shang ◽

...

Keyword(s):

Cytochrome P450 ◽

Adverse Events ◽

Success Rate ◽

Clinical Efficacy ◽

Search Algorithm ◽

Efficacy And Safety ◽

Increased Risk ◽

Significant Difference ◽

The Impact ◽

Cyp2c19 Polymorphisms

Aims: To assess the impact of cytochrome P450 (CYP) 2C19 polymorphisms on the clinical efficacy and safety of voriconazole. Methods: We systematically searched PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases from their inception to March 18, 2021 using a predefined search algorithm to identify relevant studies. Studies that reported voriconazole-treated patients and information on CYP2C19 polymorphisms were included. The efficacy outcome was success rate. The safety outcomes included overall adverse events, hepatotoxicity and neurotoxicity. Results: A total of 20 studies were included. Intermediate metabolizers (IMs) and Poor metabolizers (PMs) were associated with increased success rates compared with normal metabolizers (NMs) (risk ratio (RR): 1.18, 95% confidence interval (CI): 1.03~1.34, I2=0%, p=0.02; RR: 1.28, 95%CI: 1.06~1.54, I2=0%, p=0.01). PMs were at increased risk of overall adverse events in comparison with NMs and IMs (RR: 2.18, 95%CI: 1.35~3.53, I2=0%, p=0.001; RR: 1.80, 95% CI: 1.23~2.64, I2=0%, p=0.003). PMs demonstrated a trend towards an increased incidence of hepatotoxicity when compared with NMs (RR: 1.60, 95%CI: 0.94~2.74, I2=27%, p=0.08), although there was no statistically significant difference. In addition, there was no significant association between CYP2C19 polymorphisms and neurotoxicity. Conclusions: IMs and PMs were at a significant higher success rate in comparison with NMs. PMs were significantly associated with an increased incidence of all adverse events compared with NMs and IMs. Researches are expected to further confirm these findings. Additionally, the relationship between hepatotoxicity and CYP2C19 polymorphisms deservers clinical attention.

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CTNI-22. RETROSPECTIVE ANALYSIS OF THE COMBINED TREATMENT OF VINCRISTINE, ACNU, CARBOPLATIN AND INTERFERON-β PLUS RADIOTHERAPY (VAC-FERON-R)IN PATIENTS WITH DIFFUSE ASTROCYTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.189 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii47-ii47

Author(s):

Yoshiki Arakawa ◽

Yasuhide Makino ◽

Takeshi Kawauchi ◽

Masaharu Tanji ◽

Yohei Mineharu ◽

...

Keyword(s):

Combined Treatment ◽

Diffuse Astrocytoma ◽

Wild Type ◽

Interferon Β ◽

Mutant Type ◽

Who Grade ◽

Integrated Diagnosis ◽

Significant Difference ◽

Favorable Clinical Outcome ◽

The Impact

Abstract OBJECTIVE Diffuse astrocytomas are classified as WHO grade II and its median overall survival (mOS) is 10 to 11 years. The efficacy of chemoradiation in the high-risk feature has been reported. The prognosis is associated with IDH and TERT promoter (TERTp) mutations. Here, we retrospectively analyzed the patients with diffuse astrocytoma treated with vincristine, ACNU, carboplatin and interferon-β plus radiotherapy (VAC-feron-R)in our institute. PATIENTS AND METHODS Between December 2003 to January 2016, 44 patients were diagnosed as diffuse astrocytoma with integrated diagnosis of histological and molecular analysis. The average age was 43.1 years (22–71 years). They received VAC-feron-R as initial treatment in our institute. We analyzed the IDH1/2 and the TERTp mutation using Sangar sequencing and determined the 1p/19q codeletion by the fluorescence in situ hybridization or the multiplex ligation-dependent probe amplification. RESULTS Median follow-up period was 76.5 months, mPFS was 126 months, mOS did not reach, and 10-year survival rate was 60%.IDH status was determined in 29 patients, 9 mutant and 20 wild types. There was no significant difference in PFS and OS between the two groups. TERTp status was determined in 18 patients with IDH wild type, 6 mutant and 12 wild types. mPFS of patients with TERTp wild type did not reach, but that with TERTp mutant type was 34.5 months (p = 0.0356). CONCLUSION Compared with previous clinical studies, VAC-feron-R showed a favorable clinical outcome in diffuse astrocytoma. The impact of TERTp status on prognosis was identified but not IDH status in this cohort.

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Cost Implications of Reactive Versus Prospective Testing for Dihydropyrimidine Dehydrogenase Deficiency in Patients With Colorectal Cancer: A Single-Institution Experience

Dose-Response ◽

10.1177/1559325818803042 ◽

2018 ◽

Vol 16 (4) ◽

pp. 155932581880304 ◽

Cited By ~ 8

Author(s):

Con Murphy ◽

Stephen Byrne ◽

Gul Ahmed ◽

Andrew Kenny ◽

James Gallagher ◽

...

Keyword(s):

Colorectal Cancer ◽

Dihydropyrimidine Dehydrogenase ◽

Cost Savings ◽

Cost Effective ◽

Public Hospitals ◽

Severe Toxicity ◽

Care Payer ◽

Input Variables ◽

Grade 3 ◽

The Cost

Background: Severe toxicity is experienced by a substantial minority of patients receiving fluoropyrimidine-based chemotherapy, with approximately 20% of these severe toxicities attributable to polymorphisms in the DPYD gene. The DPYD codes for the enzyme dihydropyrimidine dehydrogenase (DPD) important in the metabolism of fluoropyrimidine-based chemotherapy. We questioned whether prospective DPYD mutation analysis in all patients commencing such therapy would prove more cost-effective than reactive testing of patients experiencing severe toxicity. Methods: All patients experiencing severe toxicity from fluoropyrimidine-based chemotherapy for colorectal cancer in an Irish private hospital over a 3-year period were tested for 4 DPYD polymorphisms previously associated with toxicity. The costs associated with an index admission for toxicity in DPD-deficient patients were examined. A cost analysis was undertaken comparing the anticipated cost of implementing screening for DPYD mutations versus current usual care. One-way sensitivity analysis was conducted on known input variables. An alternative scenario analysis from the perspective of the Irish health-care payer (responsible for public hospitals) was also performed. Results: Of 134 patients commencing first-line fluoropyrimidine chemotherapy over 3 years, 30 (23%) patients developed grade 3/4 toxicity. Of these, 17% revealed heterozygote DPYD mutations. The cost of hospitalization for the DPYD-mutated patients was €232 061, while prospectively testing all 134 patients would have cost €23 718. Prospective testing would result in cost savings across all scenarios. Conclusions: The cost of hospital admission for severe chemotherapy-related toxicity is significantly higher than the cost of prospective DPYD testing of each patient commencing fluoropyrimidine chemotherapy.

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Impact of concomitant medication use and immune-related adverse events on response to immune checkpoint inhibitors

Immunotherapy ◽

10.2217/imt-2019-0064 ◽

2020 ◽

Vol 12 (2) ◽

pp. 141-149 ◽

Cited By ~ 5

Author(s):

Shipra Gandhi ◽

Manu Pandey ◽

Nischala Ammannagari ◽

Chong Wang ◽

Mark J Bucsek ◽

...

Keyword(s):

Adverse Events ◽

Clinical Benefit ◽

Immune Checkpoint Inhibitors ◽

Concomitant Medication ◽

Checkpoint Inhibitors ◽

Metastatic Cancer ◽

Medication Use ◽

Significant Difference ◽

Β Blockers ◽

The Impact

Aim: Patients receiving checkpoint inhibitors (CPI) are frequently on other medications for co-morbidities. We explored the impact of concomitant medication use on outcomes. Materials & methods: 210 metastatic cancer patients on CPI were identified and association between concomitant medication use and immune-related adverse events with clinical outcomes was determined. Results: Aspirin, metformin, β-blockers and statins were not shown to have any statistically significant difference on clinical benefit. 26.3% patients with clinical benefit developed rash versus 11.8% without clinical benefit (p < 0.05) on multivariate analysis. Conclusion: Use of common prescription and nonprescription medications in patients with multiple co-morbidities appears safe and does not have an adverse effect on CPI efficacy. The presence of rash predicted for a better response.

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