TY - JOUR
T1 - Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma
AU - van Duin, I.A.J.
AU - Elias, S.G.
AU - van den Eertwegh, A.J.M.
AU - de Groot, J.W.B.
AU - Blokx, W.A.M.
AU - van Diest, P.J.
AU - Leiner, T.
AU - Verhoeff, J.J.C.
AU - Verheijden, R.J.
AU - van Not, O.J.
AU - Aarts, M.J.B.
AU - van den Berkmortel, F.W.P.J.
AU - Blank, C.U.
AU - Haanen, J.B.A.G.
AU - Hospers, G.A.P.
AU - Kamphuis, A.M.
AU - Piersma, D.
AU - van Rijn, R.S.
AU - van der Veldt, A.A.M.
AU - Vreugdenhil, G.
AU - Wouters, M.W.J.M.
AU - Stevense-den Boer, M.A.M.
AU - Boers-Sonderen, M.J.
AU - Kapiteijn, E.
AU - Suijkerbuijk, K.P.M.
N1 - Publisher Copyright:
© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
PY - 2023/6/15
Y1 - 2023/6/15
N2 - Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR < 2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR > 5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR 5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.
AB - Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR < 2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR > 5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR 5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.
KW - BRAF(/MEK) inhibition
KW - immune checkpoint inhibition
KW - immunotherapy
KW - melanoma
KW - prognosis
KW - SURVIVAL
U2 - 10.1002/ijc.34479
DO - 10.1002/ijc.34479
M3 - Article
C2 - 36843274
SN - 0020-7136
VL - 152
SP - 2493
EP - 2502
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 12
ER -