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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

by
Monique K. van der Kooij
1,
Marjolein J.A.L. Wetzels
1,
Maureen J.B. Aarts
2,
Franchette W.P.J. van den Berkmortel
3,
Christian U. Blank
4,
Marye J. Boers-Sonderen
5,
Miranda P. Dierselhuis
6,
Jan Willem B. de Groot
7,
Geke A.P. Hospers
8,
Djura Piersma
9,
Rozemarijn S. van Rijn
10,
Karijn P.M. Suijkerbuijk
11,
Albert J. ten Tije
12,
Astrid A.M. van der Veldt
13,
Gerard Vreugdenhil
14,
Michel W.J.M. Wouters
15,16,
John B.A.G. Haanen
4,
Alfonsus J.M. van den Eertwegh
17,
Esther Bastiaannet
18 and
Ellen Kapiteijn
1,*
1
Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, PO box 9600, 2300 RC Leiden, The Netherlands
2
Department of Medical Oncology, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands
3
Department of Medical Oncology, Zuyderland Medical Center, 6130 MB Sittard-Geleen, The Netherlands
4
Department of Medical Oncology, Netherlands Cancer Institute- Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
5
Department of Medical Oncology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB Nijmegen, The Netherlands
6
Department of Pediatric Oncology, Princess Máxima Center, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands
7
Isala Oncology Center, Isala, 8000 GK Zwolle, The Netherlands
8
Department of Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
9
Department of Medical Oncology, Medisch Spectrum Twente, Koningsplein 1, 7512 KZ Enschede, The Netherlands
10
Department of Medical Oncology, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD Leeuwarden, The Netherlands
11
Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
12
Department of Medical Oncology, Amphia Ziekenhuis, Langendijk 175, 4819 EV Breda, The Netherlands
13
Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3000 CA Rotterdam, The Netherlands
14
Department of Medical Oncology, Maxima Medical Center, de Run 4600, 5500 MB Veldhoven, The Netherlands
15
Department of Surgical Oncology, Netherlands Cancer Institute- Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
16
Scientific Bureau, Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands
17
Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands
18
Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, PO box 9600, 2300 RC Leiden, The Netherlands
 
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Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2072; https://doi.org/10.3390/cancers12082072
Received: 26 June 2020 / Revised: 17 July 2020 / Accepted: 23 July 2020 / Published: 27 July 2020
(This article belongs to the Special Issue Advanced Melanoma)
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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 (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. View Full-Text
Keywords: advanced melanoma; adolescents; young adults; AYA; BRAF mutation; checkpoint inhibitors; targeted therapy; prospective nation-wide data; outcome research; clinical audit advanced melanoma; adolescents; young adults; AYA; BRAF mutation; checkpoint inhibitors; targeted therapy; prospective nation-wide data; outcome research; clinical audit
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MDPI and ACS Style

van der Kooij, M.K.; Wetzels, M.J.A.L.; Aarts, M.J.B.; van den Berkmortel, F.W.P.J.; Blank, C.U.; Boers-Sonderen, M.J.; Dierselhuis, M.P.; de Groot, J.W.B.; Hospers, G.A.P.; Piersma, D.; van Rijn, R.S.; Suijkerbuijk, K.P.M.; ten Tije, A.J.; van der Veldt, A.A.M.; Vreugdenhil, G.; Wouters, M.W.J.M.; Haanen, J.B.A.G.; van den Eertwegh, A.J.M.; Bastiaannet, E.; Kapiteijn, E. 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. Cancers 2020, 12, 2072. https://doi.org/10.3390/cancers12082072

AMA Style

van der Kooij MK, Wetzels MJAL, Aarts MJB, van den Berkmortel FWPJ, Blank CU, Boers-Sonderen MJ, Dierselhuis MP, de Groot JWB, Hospers GAP, Piersma D, van Rijn RS, Suijkerbuijk KPM, ten Tije AJ, van der Veldt AAM, Vreugdenhil G, Wouters MWJM, Haanen JBAG, van den Eertwegh AJM, Bastiaannet E, Kapiteijn E. 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. Cancers. 2020; 12(8):2072. https://doi.org/10.3390/cancers12082072

Chicago/Turabian Style

van der Kooij, Monique K., Marjolein J.A.L. Wetzels, Maureen J.B. Aarts, Franchette W.P.J. van den Berkmortel, Christian U. Blank, Marye J. Boers-Sonderen, Miranda P. Dierselhuis, Jan W.B. de Groot, Geke A.P. Hospers, Djura Piersma, Rozemarijn S. van Rijn, Karijn P.M. Suijkerbuijk, Albert J. ten Tije, Astrid A.M. van der Veldt, Gerard Vreugdenhil, Michel W.J.M. Wouters, John B.A.G. Haanen, Alfonsus J.M. van den Eertwegh, Esther Bastiaannet, and Ellen Kapiteijn. 2020. "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" Cancers 12, no. 8: 2072. https://doi.org/10.3390/cancers12082072

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