TY - JOUR
T1 - Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients
AU - Rauwerdink, Daan Jan Willem
AU - Not, Olivier van
AU - de Meza, Melissa
AU - Doorn, Remco van
AU - Hage, Jos van der
AU - Eertwegh, A J M van den
AU - Haanen, John B
AU - Aarts, Maureen J B
AU - Berkmortel, Franchette W P J van den
AU - Blank, Christiaan U
AU - Boers-Sonderen, Marye J
AU - Groot, Jan Willem B de
AU - Hospers, Geke A P
AU - Piersma, Djura
AU - van Rijn, Rozemarijn S
AU - Stevense-den Boer, A M
AU - Veldt, Astrid A M van der
AU - Vreugdenhil, Gerard
AU - Wouters, Michel W J M
AU - Suijkerbuijk, Karijn P M
AU - Kapiteijn, Ellen
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/7/26
Y1 - 2024/7/26
N2 -
Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups.
Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development.
Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (
p < 0.01), and had a better ECOG performance status (
p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (
p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02-1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20-3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74-1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (
p < 0.01).
Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment.
AB -
Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups.
Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development.
Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (
p < 0.01), and had a better ECOG performance status (
p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (
p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02-1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20-3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74-1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (
p < 0.01).
Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment.
KW - immune checkpoint inhibitors
KW - melanoma
KW - side-effects
U2 - 10.3390/cancers16152656
DO - 10.3390/cancers16152656
M3 - Article
C2 - 39123384
SN - 2072-6694
VL - 16
JO - Cancers
JF - Cancers
IS - 15
M1 - 2656
ER -