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Observational Study
. 2022 Jan 15;150(2):317-326.
doi: 10.1002/ijc.33800. Epub 2021 Oct 2.

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

Michiel C T van Zeijl  1   2 , Alfons J M van den Eertwegh  3 , Michel W J M Wouters  1   4   5 , Liesbeth C de Wreede  5 , Maureen J B Aarts  6 , Franchette W P J van den Berkmortel  7 , Jan-Willem B de Groot  8 , Geke A P Hospers  9 , Ellen Kapiteijn  2 , Djura Piersma  10 , Rozemarijn S van Rijn  11 , Karijn P M Suijkerbuijk  12 , Albert J Ten Tije  13 , Astrid A M van der Veldt  14 , Gerard Vreugdenhil  15 , Jacobus J M van der Hoeven  16 , John B A G Haanen  17
Affiliations
Observational Study

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

Michiel C T van Zeijl et al. Int J Cancer. .

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.

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Conflict of interest statement

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.

Figures

FIGURE 1
FIGURE 1
Off‐treatment survival outcomes of patients who discontinued anti‐PD‐1 monotherapy by response status at anti‐PD‐1 discontinuation. Kaplan‐Meier curves of off‐treatment (A) progression‐free survival (log‐rank P < .0001) and (B) overall survival after anti‐PD‐1 discontinuation (log‐rank P < .001). CI, confidence interval; mo, months; NE, not estimable; OS, overall survival; PFS, progression‐free survival; prob, probability [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Competing risks analysis of second‐line treatment from anti‐PD‐1 discontinuation by response status at discontinuation, with death as competing risk. The 12‐month probabilities of second‐line treatment and death before second‐line treatment following anti‐PD‐1 discontinuation were for complete response 8.0% (95% CI = 1.8‐14) and 2.5% (95% CI = 0‐5.9); partial response 15% (95% CI = 9.0‐20) and 8.7% (95% CI = 4.4‐13); stable disease 28% (95% CI = 13‐42) and 12% (95% CI = 2.0‐23). CI, confidence interval [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Best overall response of re‐treatment with anti‐PD‐1 monotherapy in patients who relapsed after anti‐PD‐1 discontinuation. CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease
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