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. 2024 Aug 1;7(8):e2426641.
doi: 10.1001/jamanetworkopen.2024.26641.

Long-Term Survival in Patients With Advanced Melanoma

Olivier J van Not  1   2 , Alfons J M van den Eertwegh  3 , Hilde Jalving  4 , Manja Bloem  1   5   6 , John B Haanen  7 , Rozemarijn S van Rijn  8 , Maureen J B Aarts  9 , Franchette W P J van den Berkmortel  10 , Christian U Blank  7   11 , Marye J Boers-Sonderen  12 , Jan Willem de Groot J W B  13 , Geke A P Hospers  4 , Ellen Kapiteijn  14 , Brenda Leeneman  15   16 , Piersma D  17 , Marion Stevense-den Boer  18 , Astrid A M van der Veldt  19 , Gerard Vreugdenhil G  20 , Michel W J M Wouters  1   5   6 , Willeke A M Blokx  21 , Karijn P M Suijkerbuijk  2
Affiliations

Long-Term Survival in Patients With Advanced Melanoma

Olivier J van Not et al. JAMA Netw Open. .

Abstract

Importance: Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival.

Objective: To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials.

Design, setting, and participants: Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019. Data were analyzed from January to September 2023.

Exposures: Patients were treated with first-line ipilimumab-nivolumab, antibodies that target programmed cell death (anti-PD-1), or ipilimumab.

Main outcomes and measures: Progression-free survival (PFS) and melanoma-specific survival were analyzed, and a Cox proportional hazards model was used to investigate factors associated with PFS after reaching partial response (PR) or complete response (CR).

Results: A total of 2490 patients treated with first-line ICIs were included (median [IQR] age, 65.0 [55.3-73.0] years; 1561 male patients [62.7%]). Most patients had an Eastern Cooperative Oncology Group Performance Status of 1 or lower (2202 patients [88.5%]) and normal lactate dehydrogenase levels (1715 patients [68.9%]). PFS for all patients was 23.4% (95% CI, 21.7%-25.2%) after 3 years and 19.7% (95% CI, 18.0%-21.4%) after 5 years. Overall survival for all patients was 44.0% (95% CI, 42.1%-46.1%) after 3 years and 35.9% (95% CI, 33.9%-38.0%) after 5 years. Patients with metastases in 3 or more organ sites had a significantly higher hazard of progression after reaching PR or CR (adjusted hazard ratio, 1.37; 95% CI, 1.11-1.69).

Conclusions and relevance: This cohort study of patients with advanced melanoma treated with ICIs in clinical practice showed that their survival reached a plateau, comparable with patients participating in clinical trials. These findings can be used in daily clinical practice to guide long-term surveillance strategies and inform both physicians and patients regarding long-term treatment outcomes.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr van den Eertwegh reported serving on the advisory boards of Amgen, Bristol-Myers Squibb (BMS), Roche, Novartis, Merck Sharpe and Dohme (MSD) Oncology, Sanofi, Pfizer, Ipsen, Pierre Fabre, Merck, and Janssen Cilag BV; receiving grants from Sanofi, Roche, BMS, Idera, and TEVA; receiving travel funding from MSD Oncology, Roche, Pfizer, and Sanofi; and receiving speaker honoraria from BMS and Novartis, all outside the submitted work. Dr Jalving reported serving on the advisory board of Pierre Fabre outside the submitted work. Dr Haanen reported receiving grants from Asher Bio, Amgen, BioNTech, BMS, Novartis, and Sastra Cell Therapy; receiving personal fees from AstraZeneca, Achilles Therapeutics, BioNTech, BMS, CureVac, Eisai, GSK, Imcyse, Immunocore, Instil Bio, Iovance Bio, Ipsen, Merck Serono, MSD, Molecular Partners, Novartis, Neogene Therapeutics, Pfizer, PokeAcel, Roche/Genentech, Sanofi, Sastra Cell Therapy, T-Knife, and TRV; and receiving research grants from Asher Bio, Amgen, BMS, MSD, BioNTech, Neogene Therapeutics, and Novartis outside the submitted work. Dr Aarts reported serving on the advisory boards of Amgen, Astellas, Bayer, Merck, Novartis, MSD-Merck, Merck-Pfizer, BMS, Janssen, Pierre Fabre, Sanofi, and Ipson outside the submitted work. Dr Blank reported serving in advisory roles for BMS, MSD, Roche, Novartis, GSK, AstraZeneca, Pfizer, Lilly, GenMab, Pierre Fabre, and Third Rock Ventures; receiving research funding from BMS, Novartis, NanoString, and 4SC; holding stock in Immagene BV and Signature Oncology; and holding patents WO 2021/177822 A1, N2027907, and P091040NL2 all paid to institution outside the submitted work. Dr de Groot reported receiving personal fees from BMS, Pierre Fabre, Servier, MSD, and Novartis outside the submitted work. Dr Hospers reported having consultancy or advisory relationships with Amgen, BMS, Roche, MSD, Novartis, Pfizer, Sanofi, and Pierre Fabre; and has received research grants from BMS and Seerave. Dr Kapiteijn reported consultancy or advisory relationships with BMS, Novartis, Pierre Fabre, Immunocore, and Lilly; and receiving research grants from BMS, Delcath, Novartis, and Pierre-Fabre. Dr Piersma reported receiving personal fees from Pierre Fabre and Novartis outside the submitted work. Dr van Rijn reported being on the advisory board for Pfizer and receiving meeting fees from Roche. Dr van der Veldt reported receiving consultancy fees from BMS, MSD, Sanofi, Novartis, Roche, Pfizer, Eisai, Pierre Fabre, and Ipsen outside the submitted work. Dr Boers-Sonderenhas reported having consultancy or advisory relationships with Pierre Fabre, MSD, and Novartis. Dr Suijkerbuijk reported receiving grants from AbbVie, BMS, Genmab, MSD, Novartis, Philips, Sairopa SRC, TigaTx, and Pierre Fabre; receiving honoraria from Novartis; receiving research funding from BMS, Philips, Genmab, and Tiga Therapeutics; and serving on the advisory board of Abbvie outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Kaplan-Meier Curves of Progression-Free Survival (PFS), Overall Survival (OS), and Melanoma-Specific Survival (MSS)
Anti–PD-1 indicates antibodies that target programmed cell death.
Figure 2.
Figure 2.. Multivariable Cox Regression Model of Factors Associated With Progression or Death After Reaching Partial or Complete Response
Anti–PD-1 indicates antibodies that target programmed cell death; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; ICI, immune checkpoint inhibitor; LDH, lactate dehydrogenase.
See this image and copyright information in PMC

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