Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy

Katharina C. Kaehler; Christine Blome; Andrea Forschner; Ralf Gutzmer; Thomas Haalck; Lucie Heinzerling; Thomas Kornek; Elisabeth Livingstone; Carmen Loquai; Lara Valeska Maul; Berenice M. Lang; Dirk Schadendorf; Barbara Stade; Patrick Terheyden; Jochen Utikal; Tobias Wagner; Axel Hauschild; Claus Garbe; Matthias Augustin

doi:10.1097/MD.0000000000005375

Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy

Katharina C. Kaehler^*, Christine Blome, Andrea Forschner, Ralf Gutzmer, Thomas Haalck, Lucie Heinzerling, Thomas Kornek, Elisabeth Livingstone, Carmen Loquai, Lara Valeska Maul, Berenice M. Lang, Dirk Schadendorf, Barbara Stade, Patrick Terheyden, Jochen Utikal, Tobias Wagner, Axel Hauschild, Claus Garbe, Matthias Augustin

^*Corresponding author for this work

Department of Dermatology, Allergology and Venereology

16 Citations (Scopus)

Abstract

Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNa has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit. We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health). Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: diseasefree health and melanoma recurrence (with or without previous use of IFNa-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects. Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer. On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in clinical trials of new adjuvant drugs.

Original language	English
Article number	e5375
Journal	Medicine (United States)
Volume	95
Issue number	46
ISSN	0025-7974
DOIs	https://doi.org/10.1097/MD.0000000000005375
Publication status	Published - 01.01.2016

Funding

Funding/support: The study was sponsored by Merck & Co. All patients have given written informed consent, and the trial was approved by the local ethics committee. An abstract containing parts of the submitted data has been accepted as an abstract for the ASCO Annual Meeting in 2015. KCM serves as consultant to Roche, BMS, MSD and received travel grants and speaker fees from Roche, BMS, MSD, GSK, Amgen. AH serves as consultant to Roche, Novartis, Amgen, Celgene, GSK, MedImmune, MelaSciences, Merck Serono, Oncosec, Eisai and received speaker fees, travel grants, and research funding from Roche, Novartis, Amgen, Celgene, GSK, MedImmune, MelaSciences, Merck Serono, Oncosec, and Eisai. CB has received speaker honoraria, research grants, awards, and/or travel grants from Janssen-Cilag, Kreussler, Lilly, and medi. AF serves as consultant to GSK, Novartis, Roche and received travel grants and speaker fees from BMS, Roche, MSD, GSK, Novartis. RG serves as consultant to Roche, BMS, MSD, Amgen, Almirall, Leo, Pfizer, Novartis, GSK and received travel grants and speaker fees from Roche, BMS, MSD, GSK, Novartis, Merck, Almirall, Amgen, Galderma, Janssen, Boehninger and received research funding from Roche, Novartis, Johnson and Johnson, Pfizer. CG serves as consultant to Amgen, BMS, MSD, Novartis, Roche, Leo, Philogen and received travel grants and speaker fees from Amgen, BMS, MSD, Novartis, Roche, Leo, Philogen and received research funding from BMS, Novartis, Roche. TH serves as consultant to BMS and received travel grants and speaker fees from BMS, MSD, Roche and received research funding from BMS. LH serves as consultant to BMS, Roche, Merck, GSK, MSD and received travel grants and speaker fees from Roche, MSD, BMS, Roche, GSK and received research funding from BMS, MSD, GSK, Roche. TK received travel grants from MSD. Dr Livingstone serves as consultant to BMS, Boehringer-Ingelheim, Amgen and received travel grants and speaker fees from Medac, Amgen, Roche. CL serves as consultant to BMS, Roche, MSD, Novartis and received travel grants, speaker fees and speakers’ bureau fees from BMS, Roche, MSD, Novartis and received research funding from BMS, Roche, MSD, Novartis, Eisai, GSK, BioNTech. LVM received travel grants and speaker fees from BMS, MSD, IGEA, Amgen, Roche. BML received travel grants and speaker fees from Novartis and BMS. DS serves as consultant to Roche, BMS, GSK, Novartis, Amgen, Delcath, Boehringer Ingelheim, Merck, MSD, Pfizer, AstraZeneca and received travel grants, speaker fees and speakers’ bureau fees from Roche, BMS, GSK, Novartis, Amgen, Delcath, Boehringer Ingelheim, Merck, MSD, Pfizer, AstraZeneca and received research funding from Merck, BMS. BS is employed by MSD Sharp and Dohme GmbH and owned stock or held an ownership interest in Merck. PT serves as consultant to Amgen, Roche, BMS, Novartis, GSK and received travel grants and speaker fees from BMS, Roche. JU serves as consultant to GSK, Novartis, MSD, Roche and received travel grants and speakers’ bureau fees from Amgen, GSK, MSD, Novartis, and Roche. TW received travel grants from Roche Pharma AG and received research funding from B. Braun Surgical, MSD and owned stock or held an ownership interest in Bayer AG, Merck KG, Fresenius Medical Care. MA has received grants and/or honoraria as a consultant, speaker, and/or advisory board member from Almirall, GSK, and Leo.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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10.1097/MD.0000000000005375

Cite this

Kaehler, K. C., Blome, C., Forschner, A., Gutzmer, R., Haalck, T., Heinzerling, L., Kornek, T., Livingstone, E., Loquai, C., Maul, L. V., Lang, B. M., Schadendorf, D., Stade, B., Terheyden, P., Utikal, J., Wagner, T., Hauschild, A., Garbe, C., & Augustin, M. (2016). Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy. Medicine (United States), 95(46), Article e5375. https://doi.org/10.1097/MD.0000000000005375

@article{76bc08632eaa4eea95506b37ae8fbd00,

title = "Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG {"}GERMELATOX survey{"}) versus melanoma recurrence to quantify patients' relative values for adjuvant therapy",

abstract = "Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNa has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit. We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health). Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: diseasefree health and melanoma recurrence (with or without previous use of IFNa-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects. Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50\% and 75\% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer. On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in clinical trials of new adjuvant drugs.",

author = "Kaehler, \{Katharina C.\} and Christine Blome and Andrea Forschner and Ralf Gutzmer and Thomas Haalck and Lucie Heinzerling and Thomas Kornek and Elisabeth Livingstone and Carmen Loquai and Maul, \{Lara Valeska\} and Lang, \{Berenice M.\} and Dirk Schadendorf and Barbara Stade and Patrick Terheyden and Jochen Utikal and Tobias Wagner and Axel Hauschild and Claus Garbe and Matthias Augustin",

year = "2016",

month = jan,

day = "1",

doi = "10.1097/MD.0000000000005375",

language = "English",

volume = "95",

journal = "Medicine (United States)",

issn = "0025-7974",

publisher = "Lippincott Williams and Wilkins",

number = "46",

}

Kaehler, KC, Blome, C, Forschner, A, Gutzmer, R, Haalck, T, Heinzerling, L, Kornek, T, Livingstone, E, Loquai, C, Maul, LV, Lang, BM, Schadendorf, D, Stade, B, Terheyden, P, Utikal, J, Wagner, T, Hauschild, A, Garbe, C & Augustin, M 2016, 'Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy', Medicine (United States), vol. 95, no. 46, e5375. https://doi.org/10.1097/MD.0000000000005375

Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy. / Kaehler, Katharina C.; Blome, Christine; Forschner, Andrea et al.
In: Medicine (United States), Vol. 95, No. 46, e5375, 01.01.2016.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy

AU - Kaehler, Katharina C.

AU - Blome, Christine

AU - Forschner, Andrea

AU - Gutzmer, Ralf

AU - Haalck, Thomas

AU - Heinzerling, Lucie

AU - Kornek, Thomas

AU - Livingstone, Elisabeth

AU - Loquai, Carmen

AU - Maul, Lara Valeska

AU - Lang, Berenice M.

AU - Schadendorf, Dirk

AU - Stade, Barbara

AU - Terheyden, Patrick

AU - Utikal, Jochen

AU - Wagner, Tobias

AU - Hauschild, Axel

AU - Garbe, Claus

AU - Augustin, Matthias

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNa has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit. We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health). Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: diseasefree health and melanoma recurrence (with or without previous use of IFNa-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects. Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer. On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in clinical trials of new adjuvant drugs.

AB - Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNa has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit. We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health). Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: diseasefree health and melanoma recurrence (with or without previous use of IFNa-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects. Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer. On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in clinical trials of new adjuvant drugs.

UR - https://www.scopus.com/pages/publications/85012024861

U2 - 10.1097/MD.0000000000005375

DO - 10.1097/MD.0000000000005375

M3 - Journal articles

C2 - 27861370

AN - SCOPUS:85012024861

SN - 0025-7974

VL - 95

JO - Medicine (United States)

JF - Medicine (United States)

IS - 46

M1 - e5375

ER -

Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy

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Funding

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Research Areas and Centers

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