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. 2020 Dec 15;147(12):3461-3470.
doi: 10.1002/ijc.33162. Epub 2020 Jul 4.

Real-world outcomes of advanced melanoma patients not represented in phase III trials

Michiel C T van Zeijl  1   2 , Rawa K Ismail  1   3   4 , Liesbeth C de Wreede  5 , Alfonsus J M van den Eertwegh  6 , Anthonius de Boer  3   4 , Maaike van Dartel  4 , Doranne L Hilarius  7 , Maureen J B Aarts  8 , Franchette W P J van den Berkmortel  9 , Marye J Boers-Sonderen  10 , Jan-Willem B de Groot  11 , Geke A P Hospers  12 , Ellen Kapiteijn  2 , Djura Piersma  13 , Rozemarijn S van Rijn  14 , Karijn P M Suijkerbuijk  15 , Albert J Ten Tije  16 , Astrid A M van der Veldt  17 , Gerard Vreugdenhil  18 , John B A G Haanen  19 , Michel W J M Wouters  1   20
Affiliations

Real-world outcomes of advanced melanoma patients not represented in phase III trials

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

Abstract

The aim was to provide evidence on systemically treated patients with advanced melanoma not represented in phase III trials to support clinical decision-making. Analysis were performed on advanced melanoma patients diagnosed between 2014 and 2017 in the Netherlands, treated with immune- or targeted therapy, who met ≥1 trial exclusion criteria. These criteria were derived from the KEYNOTE-006 and CHECKMATE-067/-066 phase III trials. Prognostic importance of factors associated with overall survival (OS) was assessed with the Kaplan-Meier method, Cox models, predicted OS probabilities of prognostic subgroups and a conditional inference survival tree (CIST). A nationwide population-based registry was used as data source. Of 2536 systemically treated patients with advanced melanoma, 1004 (40%) patients were ineligible for phase IIII trials. Ineligible patients had a poorer median OS (mOS) compared to eligible patients (8.8 vs 23 months). Eligibility criteria strongly associated with OS in systemically treated ineligible patients were Eastern Cooperative Oncology Group Performance Score (ECOG PS) ≥2, brain metastases (BM) and lactate dehydrogenase (LDH) of >500 U/L. Patients with ECOG PS of ≥2 with or without symptomatic BM had a predicted mOS of 6.5 and 11.3 months and a 3-year survival probability of 9.3% and 23.6%, respectively. The CIST showed the strongest prognostic covariate for survival was LDH, followed by ECOG PS. The prognosis of patients with LDH of >500 U/L is poor, but long-term survival is possible. The prognosis of ineligible patients with advanced melanoma in real-world was very heterogeneous and highly dependent on LDH value, ECOG PS and symptomatic BM.

Keywords: advanced melanoma; decision tree; ineligibility; real-world outcomes; survival.

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Conflict of interest statement

A. J. M. v. d. E. 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 article from Sanofi, Roche, Bristol‐Myers Squibb, Idera and TEVA, travel expenses from MSD Oncology, Roche, Pfizer and Sanofi and received speaker honoraria from BMS and Novartis. M. J. B. S. has consultancy relationships with Pierre Fabre, MSD and Novartis. J. W. B. d. G. has advisory relationships with Bristol‐Myers Squibb, Pierre Fabre, Servier, MSD, and Novartis. G. A. P. H. has consultancy/advisory relationships with Amgen, Bristol‐Myers Squibb, Roche, MSD, Pfizer, Novartis, Pierre Fabre and has received research grants not related to this article from Bristol‐Myers Squibb, Seerave. E. K. has consultancy/advisory relationships with Bristol‐Myers Squibb, Novartis, Merck, Pierre Fabre and received research grants not related to this article from Bristol‐Myers Squibb. K. P. M. S. has consultancy/advisory relationships with Bristol‐Myers Squibb, Novartis, MSD, Pierre Fabre and received honoraria from Novartis, MSD and Roche. A. A. M. v. d. V. has consultancy/advisory relationships with Bristol‐Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai, Merck. J. B. A. G. H. has advisory relationships with Aimm, Achilles Therapeutics, Amgen, AstraZeneca, Bayer, Bristol‐Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neogene Thereapeutics, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, Vaximm and has received research grants not related to this article from Bristol‐Myers Squibb, MSD, Neon 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. All remaining authors have declared no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Overall survival of systemically treated ineligible and eligible patients estimated with the Kaplan‐Meier method [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
First‐ and second‐line systemic treatment of ineligible patients [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Conditional inference survival tree incorporating disease and patient variables into prognostic models for survival, based on year of diagnosis, age, gender, ECOG PS, LDH level, distant metastases, brain‐ and liver metastases and BRAF mutational status. P‐values are from log‐rank statistics
See this image and copyright information in PMC

References

    1. Ugurel S, Röhmel J, Ascierto PA, et al. Survival of patients with advanced metastatic melanoma: the impact of novel therapies–update 2017. Eur J Cancer. 2017;83:247‐257. - PubMed
    1. Donia M, Kimper‐Karl ML, Høyer KL, Bastholt L, Schmidt H, Svane IM. The majority of patients with metastatic melanoma are not represented in pivotal phase III immunotherapy trials. Eur J Cancer. 2017;74:89‐95. - PubMed
    1. Donia M, Ellebaek E, Øllegaard TH, et al. The real‐world impact of modern treatments on the survival of patients with metastatic melanoma. Eur J Cancer. 2019;108:25‐32. - PubMed
    1. Schadendorf D, Wolchok JD, Stephen Hodi F, et al. Efficacy and safety outcomes in patients with advanced melanoma who discontinued treatment with nivolumab and ipilimumab because of adverse events: a pooled analysis of randomized phase II and III trials. J Clin Oncol. 2017;35:3807‐3814. - PMC - PubMed
    1. Daud A, Tsai K. Management of Treatment‐Related Adverse Events with agents targeting the MAPK pathway in patients with metastatic melanoma. Oncologist. 2017;22:823‐833. - PMC - PubMed

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