Discontinuation of anti-PD-1 monotherapy in advanced melanoma-Outcomes of daily clinical practice

M.C.T. van Zeijl; A.J.M. van den Eertwegh; M.W.J.M. Wouters; L.C. de Wreede; M.J.B. Aarts; F.W.P.J. van den Berkmortel; J.W.B. de Groot; G.A.P. Hospers; E. Kapiteijn; D. Piersma; R.S. van Rijn; K.P.M. Suijkerbuijk; A.J. ten Tije; A.A.M. van der Veldt; G. Vreugdenhil; J.J.M. van der Hoeven; J.B.A.G. Haanen

doi:10.1002/ijc.33800

Discontinuation of anti-PD-1 monotherapy in advanced melanoma-Outcomes of daily clinical practice

M.C.T. van Zeijl, A.J.M. van den Eertwegh, M.W.J.M. Wouters, L.C. de Wreede, M.J.B. Aarts, F.W.P.J. van den Berkmortel, J.W.B. de Groot, G.A.P. Hospers, E. Kapiteijn, D. Piersma, R.S. van Rijn, K.P.M. Suijkerbuijk, A.J. ten Tije, A.A.M. van der Veldt, G. Vreugdenhil, J.J.M. van der Hoeven, J.B.A.G. Haanen^*

^*Corresponding author for this work

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

Abstract

There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation.

Original language	English
Pages (from-to)	317-326
Number of pages	10
Journal	International Journal of Cancer
Volume	150
Issue number	2
Early online date	2 Oct 2021
DOIs	https://doi.org/10.1002/ijc.33800
Publication status	Published - 15 Jan 2022

Keywords

advanced melanoma
anti-PD-1
discontinuation
immunotherapy
real-world
METASTATIC MELANOMA
SURVIVAL
PEMBROLIZUMAB
IPILIMUMAB

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van Zeijl, M. C. T., van den Eertwegh, A. J. M., Wouters, M. W. J. M., de Wreede, L. C., Aarts, M. J. B., van den Berkmortel, F. W. P. J., de Groot, J. W. B., Hospers, G. A. P., Kapiteijn, E., Piersma, D., van Rijn, R. S., Suijkerbuijk, K. P. M., ten Tije, A. J., van der Veldt, A. A. M., Vreugdenhil, G., van der Hoeven, J. J. M., & Haanen, J. B. A. G. (2022). Discontinuation of anti-PD-1 monotherapy in advanced melanoma-Outcomes of daily clinical practice. International Journal of Cancer, 150(2), 317-326. https://doi.org/10.1002/ijc.33800

@article{a9949cc6ce3243dcaa7addea2397e7cd,

title = "Discontinuation of anti-PD-1 monotherapy in advanced melanoma-Outcomes of daily clinical practice",

abstract = "There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation.",

keywords = "advanced melanoma, anti-PD-1, discontinuation, immunotherapy, real-world, METASTATIC MELANOMA, SURVIVAL, PEMBROLIZUMAB, IPILIMUMAB",

author = "{van Zeijl}, M.C.T. and {van den Eertwegh}, A.J.M. and M.W.J.M. Wouters and {de Wreede}, L.C. and M.J.B. Aarts and {van den Berkmortel}, F.W.P.J. and {de Groot}, J.W.B. and G.A.P. Hospers and E. Kapiteijn and D. Piersma and {van Rijn}, R.S. and K.P.M. Suijkerbuijk and {ten Tije}, A.J. and {van der Veldt}, A.A.M. and G. Vreugdenhil and {van der Hoeven}, J.J.M. and J.B.A.G. Haanen",

note = "Funding Information: Alfons J. M. van den Eertwegh has received study grants for Sanofi, Roche, Bristol-Myers Squibb, TEVA, Idera; travel expenses from MSD Oncology, Roche, Pfizer, Sanofi; speaker honoraria from Bristol-Myers Squibb, Novartis; advisory relationships with Bristol-Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck and Pierre Fabre. Jan-Willem B. de Groot has advisory relationships with Bristol-Myers Squibb, MSD, Pierre Fabre, Servier. Geke A. P. Hospers has advisory relationships with MSD, Bristol-Myers Squibb, Pfizer, Novartis; received research grant from Bristol-Myers Squibb, Seerave. Karijn P. M. Suijkerbuijk has advisory relationships with Bristol-Myers Squibb, Novartis, MSD, Pierre Fabre, Abbvie; received honoraria from MSD, Roche and Novartis. Astrid A.M. van der Veldt has consultancy relationships with Bristol-Myers Squibb, MSD, Merck, Eisai, Sanofi, Pfizer, Novartis, Ipsen, Roche. John B. A. G. Haanen has advisory relationships with Achilles Tx, BioNTech, Bristol-Myers Squibb, Immunocore, MSD, Merck Serono, Molecular Partners, Novartis, Pfizer, PokeAcel, Roche, Sanofi, T-Knife, Third Rock Ventures, Neogene Tx (including stock options); received research grants from Asher Bio, Amgen, Bristol-Myers Squibb, BioNTech, MSD, Novartis. Maureen J. B. Aarts has advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Merck, Astellas; received research grants from Pfizer. All grants/fees were not related to this article and paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication. All remaining authors have declared no conflicts of interest. Funding Information: Alfons J. M. van den Eertwegh has received study grants for Sanofi, Roche, Bristol‐Myers Squibb, TEVA, Idera; travel expenses from MSD Oncology, Roche, Pfizer, Sanofi; speaker honoraria from Bristol‐Myers Squibb, Novartis; advisory relationships with Bristol‐Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck and Pierre Fabre. Jan‐Willem B. de Groot has advisory relationships with Bristol‐Myers Squibb, MSD, Pierre Fabre, Servier. Geke A. P. Hospers has advisory relationships with MSD, Bristol‐Myers Squibb, Pfizer, Novartis; received research grant from Bristol‐Myers Squibb, Seerave. Karijn P. M. Suijkerbuijk has advisory relationships with Bristol‐Myers Squibb, Novartis, MSD, Pierre Fabre, Abbvie; received honoraria from MSD, Roche and Novartis. Astrid A.M. van der Veldt has consultancy relationships with Bristol‐Myers Squibb, MSD, Merck, Eisai, Sanofi, Pfizer, Novartis, Ipsen, Roche. John B. A. G. Haanen has advisory relationships with Achilles Tx, BioNTech, Bristol‐Myers Squibb, Immunocore, MSD, Merck Serono, Molecular Partners, Novartis, Pfizer, PokeAcel, Roche, Sanofi, T‐Knife, Third Rock Ventures, Neogene Tx (including stock options); received research grants from Asher Bio, Amgen, Bristol‐Myers Squibb, BioNTech, MSD, Novartis. Maureen J. B. Aarts has advisory relationships with Amgen, Bristol‐Myers Squibb, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Merck, Astellas; received research grants from Pfizer. All grants/fees were not related to this article and paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication. 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 governmental organisation 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 funding of the DMTR in 2019. For this work, no funding was granted Funding information Publisher Copyright: {\textcopyright} 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.",

year = "2022",

month = jan,

day = "15",

doi = "10.1002/ijc.33800",

language = "English",

volume = "150",

pages = "317--326",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "Wiley",

number = "2",

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van Zeijl, MCT, van den Eertwegh, AJM, Wouters, MWJM, de Wreede, LC, Aarts, MJB, van den Berkmortel, FWPJ, de Groot, JWB, Hospers, GAP, Kapiteijn, E, Piersma, D, van Rijn, RS, Suijkerbuijk, KPM, ten Tije, AJ, van der Veldt, AAM, Vreugdenhil, G, van der Hoeven, JJM & Haanen, JBAG 2022, 'Discontinuation of anti-PD-1 monotherapy in advanced melanoma-Outcomes of daily clinical practice', International Journal of Cancer, vol. 150, no. 2, pp. 317-326. https://doi.org/10.1002/ijc.33800

TY - JOUR

T1 - Discontinuation of anti-PD-1 monotherapy in advanced melanoma-Outcomes of daily clinical practice

AU - van Zeijl, M.C.T.

AU - van den Eertwegh, A.J.M.

AU - Wouters, M.W.J.M.

AU - de Wreede, L.C.

AU - Aarts, M.J.B.

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

AU - de Groot, J.W.B.

AU - Hospers, G.A.P.

AU - Kapiteijn, E.

AU - Piersma, D.

AU - van Rijn, R.S.

AU - Suijkerbuijk, K.P.M.

AU - ten Tije, A.J.

AU - van der Veldt, A.A.M.

AU - Vreugdenhil, G.

AU - van der Hoeven, J.J.M.

AU - Haanen, J.B.A.G.

N1 - Funding Information: Alfons J. M. van den Eertwegh has received study grants for Sanofi, Roche, Bristol-Myers Squibb, TEVA, Idera; travel expenses from MSD Oncology, Roche, Pfizer, Sanofi; speaker honoraria from Bristol-Myers Squibb, Novartis; advisory relationships with Bristol-Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck and Pierre Fabre. Jan-Willem B. de Groot has advisory relationships with Bristol-Myers Squibb, MSD, Pierre Fabre, Servier. Geke A. P. Hospers has advisory relationships with MSD, Bristol-Myers Squibb, Pfizer, Novartis; received research grant from Bristol-Myers Squibb, Seerave. Karijn P. M. Suijkerbuijk has advisory relationships with Bristol-Myers Squibb, Novartis, MSD, Pierre Fabre, Abbvie; received honoraria from MSD, Roche and Novartis. Astrid A.M. van der Veldt has consultancy relationships with Bristol-Myers Squibb, MSD, Merck, Eisai, Sanofi, Pfizer, Novartis, Ipsen, Roche. John B. A. G. Haanen has advisory relationships with Achilles Tx, BioNTech, Bristol-Myers Squibb, Immunocore, MSD, Merck Serono, Molecular Partners, Novartis, Pfizer, PokeAcel, Roche, Sanofi, T-Knife, Third Rock Ventures, Neogene Tx (including stock options); received research grants from Asher Bio, Amgen, Bristol-Myers Squibb, BioNTech, MSD, Novartis. Maureen J. B. Aarts has advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Merck, Astellas; received research grants from Pfizer. All grants/fees were not related to this article and paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication. All remaining authors have declared no conflicts of interest. Funding Information: Alfons J. M. van den Eertwegh has received study grants for Sanofi, Roche, Bristol‐Myers Squibb, TEVA, Idera; travel expenses from MSD Oncology, Roche, Pfizer, Sanofi; speaker honoraria from Bristol‐Myers Squibb, Novartis; advisory relationships with Bristol‐Myers Squibb, MSD Oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck and Pierre Fabre. Jan‐Willem B. de Groot has advisory relationships with Bristol‐Myers Squibb, MSD, Pierre Fabre, Servier. Geke A. P. Hospers has advisory relationships with MSD, Bristol‐Myers Squibb, Pfizer, Novartis; received research grant from Bristol‐Myers Squibb, Seerave. Karijn P. M. Suijkerbuijk has advisory relationships with Bristol‐Myers Squibb, Novartis, MSD, Pierre Fabre, Abbvie; received honoraria from MSD, Roche and Novartis. Astrid A.M. van der Veldt has consultancy relationships with Bristol‐Myers Squibb, MSD, Merck, Eisai, Sanofi, Pfizer, Novartis, Ipsen, Roche. John B. A. G. Haanen has advisory relationships with Achilles Tx, BioNTech, Bristol‐Myers Squibb, Immunocore, MSD, Merck Serono, Molecular Partners, Novartis, Pfizer, PokeAcel, Roche, Sanofi, T‐Knife, Third Rock Ventures, Neogene Tx (including stock options); received research grants from Asher Bio, Amgen, Bristol‐Myers Squibb, BioNTech, MSD, Novartis. Maureen J. B. Aarts has advisory relationships with Amgen, Bristol‐Myers Squibb, Novartis, MSD, Pierre Fabre, Sanofi, Pfizer, Ipsen, Merck, Astellas; received research grants from Pfizer. All grants/fees were not related to this article and paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication. 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 governmental organisation 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 funding of the DMTR in 2019. For this work, no funding was granted Funding information Publisher Copyright: © 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

PY - 2022/1/15

Y1 - 2022/1/15

N2 - There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation.

AB - There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation.

KW - advanced melanoma

KW - anti-PD-1

KW - discontinuation

KW - immunotherapy

KW - real-world

KW - METASTATIC MELANOMA

KW - SURVIVAL

KW - PEMBROLIZUMAB

KW - IPILIMUMAB

U2 - 10.1002/ijc.33800

DO - 10.1002/ijc.33800

M3 - Article

C2 - 34520567

SN - 0020-7136

VL - 150

SP - 317

EP - 326

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 2

ER -