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The impact of dose and simultaneous use of acid-reducing agents on the effectiveness of vemurafenib in metastatic BRAF V600 mutated melanoma: a Retrospective Cohort Study

The impact of dose and simultaneous use of acid-reducing agents on the effectiveness of vemurafenib in metastatic BRAF V600 mutated melanoma: a Retrospective Cohort Study
The impact of dose and simultaneous use of acid-reducing agents on the effectiveness of vemurafenib in metastatic BRAF V600 mutated melanoma: a Retrospective Cohort Study

Background: The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown.

Objectives: To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs. 

Patient and Methods: A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012–March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital. Cox regression analysis was used to estimate the risk of progression with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n = 77). Analyses were adjusted for age and sex.

Results: In total, disease progression occurred in 55% of treated patients on vemurafenib, with a median progression-free survival of 6.0 (95% confidence interval [CI] 5.0–6.9) months. Compared to patients on vemurafenib alone, there was no increased risk of progression among patients requiring vemurafenib at a reduced dose or among patients receiving simultaneous therapy with vemurafenib and ARAs. In addition, there was no increased risk of progression among patients who used reduced-dose vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole therapy. However, a tendency for progression was observed among patients who used full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted hazard ratio [HRa] 2.37; 95% CI 0.97–5.76), which became statistically significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51–13.75).

Conclusions: There was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation. [Figure not available: see fulltext.]

1776-2596
363-370
Knapen, Lotte M.
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Koornstra, Rutger H.T.
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Driessen, Johanna H.M.
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van Vlijmen, Bas
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Croes, Sander
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Schalkwijk, Stein
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Colbers, Angela
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Gerritsen, Winald R.
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Burger, David M.
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de Vries, Frank
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van Erp, Nielka P.
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Knapen, Lotte M.
a2c486f6-09fa-4b02-82b8-7658d206db69
Koornstra, Rutger H.T.
6115c38e-8945-4f8d-adbb-cd16b4f598fa
Driessen, Johanna H.M.
ca186d54-4f1c-4131-ba45-78357fe592dd
van Vlijmen, Bas
809e7eb2-e2df-4827-a2a3-7139bea8aca3
Croes, Sander
2cf9e562-32ac-43ba-ba14-4523a6ca4120
Schalkwijk, Stein
76805a1f-c32f-4d46-85b1-595b71d958a0
Colbers, Angela
cc49e89d-fcaf-41e8-bfdb-68e1c25d0de9
Gerritsen, Winald R.
eeb1b541-f8d3-40df-bc95-9a163a6e360d
Burger, David M.
0dd3ff7c-2462-435c-8989-75f05891f1cb
de Vries, Frank
10245a32-6083-4feb-9d20-7e7db0f358b1
van Erp, Nielka P.
e1342d63-a3f7-4459-a400-6821556c52ce

Knapen, Lotte M., Koornstra, Rutger H.T., Driessen, Johanna H.M., van Vlijmen, Bas, Croes, Sander, Schalkwijk, Stein, Colbers, Angela, Gerritsen, Winald R., Burger, David M., de Vries, Frank and van Erp, Nielka P. (2018) The impact of dose and simultaneous use of acid-reducing agents on the effectiveness of vemurafenib in metastatic BRAF V600 mutated melanoma: a Retrospective Cohort Study. Targeted Oncology, 13 (3), 363-370. (doi:10.1007/s11523-018-0564-3).

Record type: Article

Abstract

Background: The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown.

Objectives: To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs. 

Patient and Methods: A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012–March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital. Cox regression analysis was used to estimate the risk of progression with full-dose (n = 64) versus reduced-dose vemurafenib (n = 48) and with simultaneous use of vemurafenib and ARAs (n = 35) versus vemurafenib alone (n = 77). Analyses were adjusted for age and sex.

Results: In total, disease progression occurred in 55% of treated patients on vemurafenib, with a median progression-free survival of 6.0 (95% confidence interval [CI] 5.0–6.9) months. Compared to patients on vemurafenib alone, there was no increased risk of progression among patients requiring vemurafenib at a reduced dose or among patients receiving simultaneous therapy with vemurafenib and ARAs. In addition, there was no increased risk of progression among patients who used reduced-dose vemurafenib and ARAs versus those receiving full-dose vemurafenib as sole therapy. However, a tendency for progression was observed among patients who used full-dose vemurafenib and ARAs versus full-dose vemurafenib alone (adjusted hazard ratio [HRa] 2.37; 95% CI 0.97–5.76), which became statistically significant in a sensitivity analysis (HRa 4.56; 95% CI 1.51–13.75).

Conclusions: There was no association between the use of vemurafenib in a reduced dose or the simultaneous use of vemurafenib and ARAs and the risk of progression. In addition, there was no association between the simultaneous use of vemurafenib in a reduced dose and ARAs and the risk of progression. However, patients tolerating full-dose vemurafenib simultaneously with ARAs might have an increased risk of progression. This finding requires prospective validation. [Figure not available: see fulltext.]

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e-pub ahead of print date: 11 April 2018
Published date: 1 June 2018

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Local EPrints ID: 424713
URI: https://eprints.soton.ac.uk/id/eprint/424713
ISSN: 1776-2596
PURE UUID: 01503fd1-9550-4749-9683-72737834dd6b

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Date deposited: 05 Oct 2018 11:41
Last modified: 09 Dec 2019 18:00

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Contributors

Author: Lotte M. Knapen
Author: Rutger H.T. Koornstra
Author: Johanna H.M. Driessen
Author: Bas van Vlijmen
Author: Sander Croes
Author: Stein Schalkwijk
Author: Angela Colbers
Author: Winald R. Gerritsen
Author: David M. Burger
Author: Frank de Vries
Author: Nielka P. van Erp

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