The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors

Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer

Manvi Sharma, Holly M. Holmes, Hemalkumar Mehta, Hua Chen, Rajender R. Aparasu, Ya Chen T. Shih, Sharon H. Giordano, Michael L. Johnson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer. Methods: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome. Results: The overall prevalence of TKI-PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04-1.18) but was not associated with discontinuation. Conclusions: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Proton Pump Inhibitors
Protein-Tyrosine Kinases
Survival
Neoplasms
Therapeutics
Confidence Intervals
Polypharmacy
Liver Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Medicare
Pancreatic Neoplasms
Drug Interactions
Renal Cell Carcinoma
Lung Neoplasms
Epidemiology
Retrospective Studies

Keywords

  • and End Results (SEER)-Medicare
  • drug-drug interaction
  • elderly
  • Epidemiology
  • Medicare Part D
  • polypharmacy
  • predictors
  • prevalence
  • proton pump inhibitors
  • Surveillance
  • survival
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors : Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer. / Sharma, Manvi; Holmes, Holly M.; Mehta, Hemalkumar; Chen, Hua; Aparasu, Rajender R.; Shih, Ya Chen T.; Giordano, Sharon H.; Johnson, Michael L.

In: Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Sharma, Manvi ; Holmes, Holly M. ; Mehta, Hemalkumar ; Chen, Hua ; Aparasu, Rajender R. ; Shih, Ya Chen T. ; Giordano, Sharon H. ; Johnson, Michael L. / The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors : Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer. In: Cancer. 2019.
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abstract = "Background: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer. Methods: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome. Results: The overall prevalence of TKI-PPI receipt was 22.7{\%}. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95{\%} confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95{\%} confidence interval, 1.04-1.18) but was not associated with discontinuation. Conclusions: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.",
keywords = "and End Results (SEER)-Medicare, drug-drug interaction, elderly, Epidemiology, Medicare Part D, polypharmacy, predictors, prevalence, proton pump inhibitors, Surveillance, survival, tyrosine kinase inhibitors",
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T1 - The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors

T2 - Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer

AU - Sharma, Manvi

AU - Holmes, Holly M.

AU - Mehta, Hemalkumar

AU - Chen, Hua

AU - Aparasu, Rajender R.

AU - Shih, Ya Chen T.

AU - Giordano, Sharon H.

AU - Johnson, Michael L.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer. Methods: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome. Results: The overall prevalence of TKI-PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04-1.18) but was not associated with discontinuation. Conclusions: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.

AB - Background: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer. Methods: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome. Results: The overall prevalence of TKI-PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04-1.18) but was not associated with discontinuation. Conclusions: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.

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KW - elderly

KW - Epidemiology

KW - Medicare Part D

KW - polypharmacy

KW - predictors

KW - prevalence

KW - proton pump inhibitors

KW - Surveillance

KW - survival

KW - tyrosine kinase inhibitors

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DO - 10.1002/cncr.31917

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