2 research outputs found
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
Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults
(AYAs, 15β39 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 3β4 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 3β4 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 3β4 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 0.6β0.8) was explained by the increased cumulative incidence of
non-melanoma related deaths in older adults (sub-distribution HR 2.8; 95% CI 1.5β4.9), 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