Age Does Matter in Adolescents and Young Adults versus Older Adults with Advanced Melanoma; A National Cohort Study Comparing Tumor Characteristics, Treatment Pattern, Toxicity and Response
van der Kooij, Monique K; Wetzels, Marjolein J A L; Aarts, Maureen J B; van den Berkmortel, Franchette W P J; Blank, Christian U; Boers-Sonderen, Marye J; Dierselhuis, Miranda P; de Groot, Jan Willem B; Hospers, Geke A P; Piersma, Djura; van Rijn, Rozemarijn S; Suijkerbuijk, Karijn P M; Ten Tije, Albert J; van der Veldt, Astrid A M; Vreugdenhil, Gerard; Wouters, Michel W J M; Haanen, John B A G; van den Eertwegh, Alfonsus J M; Bastiaannet, Esther; Kapiteijn, Ellen
(2020) Cancers, volume 12, issue 8, pp. 1 - 15
(Article)
Abstract
Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults (AYAs, 15-39 years of age). However, AYAs are underrepresented in clinical trials investigating new therapies and the outcomes from these therapies for AYAs are therefore unclear. Using prospectively collected nation-wide data from the Dutch Melanoma Treatment Registry
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(DMTR), we compared baseline characteristics, mutational profiles, treatment strategies, grade 3-4 adverse events (AEs), responses and outcomes in AYAs (n = 210) and older adults (n = 3775) who were diagnosed with advanced melanoma between July 2013 and July 2018. Compared to older adults, AYAs were more frequently female (51% versus 40%, p = 0.001), and had a better Eastern Cooperative Oncology Group performance status (ECOG 0 in 54% versus 45%, p = 0.004). BRAF and NRAS mutations were age dependent, with more BRAF V600 mutations in AYAs (68% versus 46%) and more NRAS mutations in older adults (13% versus 21%), p < 0.001. This finding translated in distinct first-line treatment patterns, where AYAs received more initial targeted therapy. Overall, grade 3-4 AE percentages following first-line systemic treatment were similar for AYAs and older adults; anti-PD-1 (7% versus 14%, p = 0.25), anti-CTLA-4 (16% versus 33%, p = 0.12), anti-PD-1 + anti-CTLA-4 (67% versus 56%, p = 0.34) and BRAF/MEK-inhibition (14% versus 23%, p = 0.06). Following anti-CTLA-4 treatment, no AYAs experienced a grade 3-4 colitis, while 17% of the older adults did (p = 0.046). There was no difference in response to treatment between AYAs and older adults. The longer overall survival observed in AYAs (hazard ratio (HR) 0.7; 95% CI 0.6-0.8) was explained by the increased cumulative incidence of non-melanoma related deaths in older adults (sub-distribution HR 2.8; 95% CI 1.5-4.9), calculated by competing risk analysis. The results of our national cohort study show that baseline characteristics and mutational profiles differ between AYAs and older adults with advanced melanoma, leading to different treatment choices made in daily practice. Once treatment is initiated, AYAs and older adults show similar tumor responses and melanoma-specific survival.
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Keywords: Adolescents, Advanced melanoma, AYA, BRAF mutation, Checkpoint inhibitors, Clinical audit, Outcome research, Prospective nation-wide data, Targeted therapy, Young adults, targeted therapy, adolescents, advanced melanoma, clinical audit, young adults, prospective nation-wide data, outcome research, checkpoint inhibitors, Oncology, Cancer Research, Journal Article
ISSN: 2072-6694
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: Funding: This research received no external funding. The Netherlands Organization for Health Research and Development funded the start-up of the Dutch Melanoma Treatment Registry (DMTR). Grant number: 836002002. This grant was awarded under the effectiveness research for high-cost medicine program. From its foundation, the DMTR has been sponsored by BMS, Novartis, Roche Nederland B.V., MSD, and Pierre Fabre via the Dutch Institute for Clinical Auditing (DICA). The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Funding Information: This research received no external funding. The Netherlands Organization for Health Research and Development funded the start-up of the Dutch Melanoma Treatment Registry (DMTR). Grant number 836002002. This grant was awarded under the effectiveness research for high-cost medicine program. From its foundation, the DMTR has been sponsored by BMS, Novartis, Roche Nederland B.V., MSD, and Pierre Fabre via the Dutch Institute for Clinical Auditing (DICA). The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Funding Information: Conflicts of Interest: C.U. Blank reports receiving commercial research grants from Novartis, Bristol-Myers Squibb, and NanoString; is a paid advisory board member for Bristol-Myers Squibb, MSD, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, and Pierre Fabre; and holds ownership interest in Uniti Cars, Neon Therapeutics, and Forty Seven. M.J. Boers-Sonderen has served as an advisory board member for Bristol-Myers Squibb, Novartis, Merck and Pierre Fabre. A.J.M. van den Eertwegh has served as a speaker for Bristol-Myers Squibb and Novartis and an advisory board member for Bristol-Myers Squibb, MSD oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck, Pierre Fabre and has received research grants not related to this paper from Sanofi, Roche, Bristol-Myers Squibb, TEVA and Idera. J.W. de Groot is a paid consultant for Bristol-Myers Squibb and MSD. G.A.P. Hospers is an unpaid consultant/advisory board member for Bristol-Myers Squibb, MSD, Roche, and Novartis. D. Piersma has served as an advisory board member for Amgen, BMS and Pierre Fabre. A.A.M. van der Veldt is a paid consultant for Bristol-Myers Squibb, MSD, Novartis, Roche, Pfizer, Eisai, Ipsen, Pierre Fabre, Sanofi, and Bayer. J.B.A.G. Haanen is a paid consultant for AIMM, Neon Therapeutics, Immunocore, Vaximm, and Neogene Therapeutics, and reports receiving commercial research grants from Bristol-Myers Squibb, MSD, Novartis, and Neon Therapeutics. K.P.M. Suijkerbuijk has served as a consultant and/or advisory board member for Bristol-Myers Squibb, Novartis, MSD, Pierre Fabre and AbbVie and received honoraria/research support not related to this manuscript from Novartis, Roche and MSD. All paid to institution. H.W. Kapiteijn has served as a consultant and/or advisory board member for Bristol-Myers Squibb, Novartis, Merck, Pierre Fabre and has received research grants not related to this paper from Bristol-Myers Squibb. No potential conflicts of interest were disclosed by the other authors. Publisher Copyright: © 2020, MDPI AG. All rights reserved.
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