Adjuvant treatment for melanoma in clinical practice – Trial versus reality

Melissa M. de Meza; Rawa K. Ismail; Daan Rauwerdink; Olivier J. van Not; Jesper van Breeschoten; Willeke A.M. Blokx; Anthonius de Boer; Maaike van Dartel; Doranne L. Hilarius; Eva Ellebaek; Han J. Bonenkamp; Christian U. Blank; Maureen J.B. Aarts; Alexander C.J. van Akkooi; Franchette W.P.J. van den Berkmortel; Marye J. Boers-Sonderen; Jan Willem B. de Groot; John B. Haanen; Geke A.P. Hospers; Ellen W. Kapiteijn; Djura Piersma; Roos S. van Rijn; Astrid A.M. van der Veldt; Art Vreugdenhil; Hans M. Westgeest; Alfons J.M. van den Eertwegh; Karijn P.M. Suijkerbuijk; Michel W.J.M. Wouters

doi:10.1016/j.ejca.2021.08.044

Adjuvant treatment for melanoma in clinical practice – Trial versus reality

Melissa M. de Meza^*, Rawa K. Ismail, Daan Rauwerdink, Olivier J. van Not, Jesper van Breeschoten, Willeke A.M. Blokx, Anthonius de Boer, Maaike van Dartel, Doranne L. Hilarius, Eva Ellebaek, Han J. Bonenkamp, Christian U. Blank, Maureen J.B. Aarts, Alexander C.J. van Akkooi, Franchette W.P.J. van den Berkmortel, Marye J. Boers-Sonderen, Jan Willem B. de Groot, John B. Haanen, Geke A.P. Hospers, Ellen W. KapiteijnDjura Piersma, Roos S. van Rijn, Astrid A.M. van der Veldt, Art Vreugdenhil, Hans M. Westgeest, Alfons J.M. van den Eertwegh, Karijn P.M. Suijkerbuijk, Michel W.J.M. Wouters

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting. Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan–Meier method. Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9–74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade ≥3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy. Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials.

Original language	English
Pages (from-to)	234-245
Number of pages	12
Journal	European Journal of Cancer
Volume	158
DOIs	https://doi.org/10.1016/j.ejca.2021.08.044
Publication status	Published - Nov 2021

Keywords

Data management
Immune checkpoint inhibitors
Immunotherapy
Melanoma
Nivolumab
Pembrolizumab
Quality of health care
Registries
Skin neoplasms
Survival rate

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de Meza, M. M., Ismail, R. K., Rauwerdink, D., van Not, O. J., van Breeschoten, J., Blokx, W. A. M., de Boer, A., van Dartel, M., Hilarius, D. L., Ellebaek, E., Bonenkamp, H. J., Blank, C. U., Aarts, M. J. B., van Akkooi, A. C. J., van den Berkmortel, F. W. P. J., Boers-Sonderen, M. J., de Groot, J. W. B., Haanen, J. B., Hospers, G. A. P., ... Wouters, M. W. J. M. (2021). Adjuvant treatment for melanoma in clinical practice – Trial versus reality. European Journal of Cancer, 158, 234-245. https://doi.org/10.1016/j.ejca.2021.08.044

@article{9fa8243d856344bb8f8d8479ca43aa00,

title = "Adjuvant treatment for melanoma in clinical practice – Trial versus reality",

abstract = "Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting. Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan–Meier method. Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9–74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade ≥3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy. Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials.",

keywords = "Data management, Immune checkpoint inhibitors, Immunotherapy, Melanoma, Nivolumab, Pembrolizumab, Quality of health care, Registries, Skin neoplasms, Survival rate",

author = "{de Meza}, {Melissa M.} and Ismail, {Rawa K.} and Daan Rauwerdink and {van Not}, {Olivier J.} and {van Breeschoten}, Jesper and Blokx, {Willeke A.M.} and {de Boer}, Anthonius and {van Dartel}, Maaike and Hilarius, {Doranne L.} and Eva Ellebaek and Bonenkamp, {Han J.} and Blank, {Christian U.} and Aarts, {Maureen J.B.} and {van Akkooi}, {Alexander C.J.} and {van den Berkmortel}, {Franchette W.P.J.} and Boers-Sonderen, {Marye J.} and {de Groot}, {Jan Willem B.} and Haanen, {John B.} and Hospers, {Geke A.P.} and Kapiteijn, {Ellen W.} and Djura Piersma and {van Rijn}, {Roos S.} and {van der Veldt}, {Astrid A.M.} and Art Vreugdenhil and Westgeest, {Hans M.} and {van den Eertwegh}, {Alfons J.M.} and Suijkerbuijk, {Karijn P.M.} and Wouters, {Michel W.J.M.}",

note = "Funding Information: AvdE has advisory relationships with Amgen, Bristol Myers Squibb, Roche, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Merck and has received research study grants not related to this paper from Sanofi, Roche, Bristol Myers Squibb, Idera and TEVA and has received travel expenses from MSD Oncology, Roche, Pfizer and Sanofi and has received speaker honoraria from BMS and Novartis. MBS has consultancy/advisory relationships with Pierre Fabre, MSD and Novartis. JdG has consultancy/advisory relationships with Bristol Myers Squibb, Pierre Fabre, Servier, MSD, Novartis. GH consultancy/advisory relationships with Amgen, Bristol Myers Squibb, Roche, MSD, Pfizer, Novartis, Pierre Fabre and has received research grants not related to this paper from Bristol Myers Squibb, Seerave. EK has consultancy/advisory relationships with BristolMyers Squibb, Novartis, Merck, Pierre Fabre, and received research grants not related to this paper from Bristol Myers Squibb. KS has advisory relationships with Bristol Myers Squibb, Novartis, MSD, Pierre Fabre, Abbvie and received honoraria from Novartis, MSD and Roche. AvdV has consultancy relationships with Bristol Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai, Merck. JH has advisory relationships with Achilles Therapeutics, Bristol Myers Squibb, BioNTech, Immunocore, Ipsen, MSD, Merck Serono, Molecular Partners, Novartis, Neogene Therapeutics, PokeAcel, Pfizer, Roche/Genentech, Sanofi, T-Knife, Third Rock Ventures, and has received research grants not related to this paper from Amgen, Bristol Myers Squibb, MSD, BioNTech, Neogene Therapeutics and Novartis. All grants were paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication. AvA has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC. Research grants from Amgen, Merck-Pfizer. All outside of current work and all paid to institute. MA has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, Bayer. Research grants Merck-Pfizer. Not related to current work and paid to institute. HMW has received travel expenses from Ipsen and Astellas and has received honoraria from Roche and Astellas. RvR has received expert meeting fees from Roche and advisory board fees from Pfizer. EE has received speaker honoraria from BMS, Pierre Fabre, Kyowa Kirin, and travel/conference expenses from MSD. All remaining authors have declared no conflicts of interest. Funding Information: For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from the governmental organization The Netherlands Organization for Health Research and Development (ZonMW, grant number 836002002 ). The DMTR is structurally funded by Bristol Myers Squibb , Merck Sharpe & Dohme , Novartis and Roche Pharma . Roche Pharma stopped and Pierre Fabre started the funding of the DMTR in 2019. For this work, no funding was granted. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = nov,

doi = "10.1016/j.ejca.2021.08.044",

language = "English",

volume = "158",

pages = "234--245",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd",

}

de Meza, MM, Ismail, RK, Rauwerdink, D, van Not, OJ, van Breeschoten, J, Blokx, WAM, de Boer, A, van Dartel, M, Hilarius, DL, Ellebaek, E, Bonenkamp, HJ, Blank, CU, Aarts, MJB, van Akkooi, ACJ, van den Berkmortel, FWPJ, Boers-Sonderen, MJ, de Groot, JWB, Haanen, JB, Hospers, GAP, Kapiteijn, EW, Piersma, D, van Rijn, RS, van der Veldt, AAM, Vreugdenhil, A, Westgeest, HM, van den Eertwegh, AJM, Suijkerbuijk, KPM & Wouters, MWJM 2021, 'Adjuvant treatment for melanoma in clinical practice – Trial versus reality', European Journal of Cancer, vol. 158, pp. 234-245. https://doi.org/10.1016/j.ejca.2021.08.044

TY - JOUR

T1 - Adjuvant treatment for melanoma in clinical practice – Trial versus reality

AU - de Meza, Melissa M.

AU - Ismail, Rawa K.

AU - Rauwerdink, Daan

AU - van Not, Olivier J.

AU - van Breeschoten, Jesper

AU - Blokx, Willeke A.M.

AU - de Boer, Anthonius

AU - van Dartel, Maaike

AU - Hilarius, Doranne L.

AU - Ellebaek, Eva

AU - Bonenkamp, Han J.

AU - Blank, Christian U.

AU - Aarts, Maureen J.B.

AU - van Akkooi, Alexander C.J.

AU - van den Berkmortel, Franchette W.P.J.

AU - Boers-Sonderen, Marye J.

AU - de Groot, Jan Willem B.

AU - Haanen, John B.

AU - Hospers, Geke A.P.

AU - Kapiteijn, Ellen W.

AU - Piersma, Djura

AU - van Rijn, Roos S.

AU - van der Veldt, Astrid A.M.

AU - Vreugdenhil, Art

AU - Westgeest, Hans M.

AU - van den Eertwegh, Alfons J.M.

AU - Suijkerbuijk, Karijn P.M.

AU - Wouters, Michel W.J.M.

N1 - Funding Information: AvdE has advisory relationships with Amgen, Bristol Myers Squibb, Roche, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Merck and has received research study grants not related to this paper from Sanofi, Roche, Bristol Myers Squibb, Idera and TEVA and has received travel expenses from MSD Oncology, Roche, Pfizer and Sanofi and has received speaker honoraria from BMS and Novartis. MBS has consultancy/advisory relationships with Pierre Fabre, MSD and Novartis. JdG has consultancy/advisory relationships with Bristol Myers Squibb, Pierre Fabre, Servier, MSD, Novartis. GH consultancy/advisory relationships with Amgen, Bristol Myers Squibb, Roche, MSD, Pfizer, Novartis, Pierre Fabre and has received research grants not related to this paper from Bristol Myers Squibb, Seerave. EK has consultancy/advisory relationships with BristolMyers Squibb, Novartis, Merck, Pierre Fabre, and received research grants not related to this paper from Bristol Myers Squibb. KS has advisory relationships with Bristol Myers Squibb, Novartis, MSD, Pierre Fabre, Abbvie and received honoraria from Novartis, MSD and Roche. AvdV has consultancy relationships with Bristol Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai, Merck. JH has advisory relationships with Achilles Therapeutics, Bristol Myers Squibb, BioNTech, Immunocore, Ipsen, MSD, Merck Serono, Molecular Partners, Novartis, Neogene Therapeutics, PokeAcel, Pfizer, Roche/Genentech, Sanofi, T-Knife, Third Rock Ventures, and has received research grants not related to this paper from Amgen, Bristol Myers Squibb, MSD, BioNTech, Neogene Therapeutics and Novartis. All grants were paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication. AvA has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC. Research grants from Amgen, Merck-Pfizer. All outside of current work and all paid to institute. MA has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, Bayer. Research grants Merck-Pfizer. Not related to current work and paid to institute. HMW has received travel expenses from Ipsen and Astellas and has received honoraria from Roche and Astellas. RvR has received expert meeting fees from Roche and advisory board fees from Pfizer. EE has received speaker honoraria from BMS, Pierre Fabre, Kyowa Kirin, and travel/conference expenses from MSD. All remaining authors have declared no conflicts of interest. Funding Information: For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from the governmental organization The Netherlands Organization for Health Research and Development (ZonMW, grant number 836002002 ). The DMTR is structurally funded by Bristol Myers Squibb , Merck Sharpe & Dohme , Novartis and Roche Pharma . Roche Pharma stopped and Pierre Fabre started the funding of the DMTR in 2019. For this work, no funding was granted. Publisher Copyright: © 2021 The Authors

PY - 2021/11

Y1 - 2021/11

N2 - Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting. Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan–Meier method. Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9–74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade ≥3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy. Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials.

AB - Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting. Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan–Meier method. Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9–74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade ≥3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy. Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials.

KW - Data management

KW - Immune checkpoint inhibitors

KW - Immunotherapy

KW - Melanoma

KW - Nivolumab

KW - Pembrolizumab

KW - Quality of health care

KW - Registries

KW - Skin neoplasms

KW - Survival rate

UR - http://www.scopus.com/inward/record.url?scp=85116049321&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2021.08.044

DO - 10.1016/j.ejca.2021.08.044

M3 - Article

AN - SCOPUS:85116049321

SN - 0959-8049

VL - 158

SP - 234

EP - 245

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Adjuvant treatment for melanoma in clinical practice – Trial versus reality

Abstract

Keywords

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