TY - JOUR
T1 - Pooled Long-Term Outcomes with Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients with Advanced Melanoma
AU - Long, Georgina V.
AU - Larkin, James
AU - Schadendorf, Dirk
AU - Grob, Jean Jacques
AU - Lao, Christopher D.
AU - Márquez-Rodas, Iván
AU - Wagstaff, John
AU - Lebbé, Céleste
AU - Pigozzo, Jacopo
AU - Robert, Caroline
AU - Ascierto, Paolo A.
AU - Atkinson, Victoria
AU - Postow, Michael A.
AU - Atkins, Michael B.
AU - Sznol, Mario
AU - Callahan, Margaret K.
AU - Topalian, Suzanne L.
AU - Sosman, Jeffrey A.
AU - Kotapati, Srividya
AU - Thakkar, Pratik K.
AU - Ritchings, Corey
AU - Pe Benito, Melanie
AU - Re, Sandra
AU - Soleymani, Samira
AU - Hodi, F. Stephen
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2025/3/10
Y1 - 2025/3/10
N2 - PURPOSE Nivolumab (NIVO) ipilimumab (IPI) combination and NIVO monotherapy have demonstrated durable clinical benefit in patients with unresectable/metastatic melanoma. This analysis describes long-term overall survival (OS) with the combination or monotherapy pooled across all major company-sponsored trials, as well as clinical factors associated with survival, in patients with immune checkpoint inhibitor (ICI) treatment-naïve unresectable/metastatic melanoma.METHODSData were pooled from six CheckMate studies in ICI treatment-naïve patients receiving NIVO + IPI (NIVO 1 mg/kg + IPI 3 mg/kg or NIVO 3 mg/kg + IPI 1 mg/kg) or NIVO monotherapy (3 mg/kg). OS was assessed for each treatment, as well as in select subgroups. Cox proportional multivariate analysis (MVA) and classification and regression tree (CART) analyses were performed within treatment arms.RESULTSMedian follow-up for OS was 45.0 months for patients treated with NIVO + IPI (n = 839) and 35.8 months for patients treated with NIVO (n = 536). OS was longer with NIVO + IPI versus NIVO monotherapy (hazard ratio, 0.78 [95% CI, 0.67 to 0.91]), with 6-year OS rates of 52% versus 41%, respectively. Consistent benefit was observed in BRAF-mutant and BRAF-wild-type patients and those with normal and elevated lactate dehydrogenase (LDH). Numerical difference in OS was also observed across PD-L1 expression levels, although more pronounced with no/low PD-L1 expression. Clinical factors associated with decreased survival in both the MVA and CART analyses were LDH > upper limit of normal with either treatment, age ≥65 years with NIVO + IPI, and the presence of liver metastases with NIVO monotherapy.CONCLUSIONIn this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.
AB - PURPOSE Nivolumab (NIVO) ipilimumab (IPI) combination and NIVO monotherapy have demonstrated durable clinical benefit in patients with unresectable/metastatic melanoma. This analysis describes long-term overall survival (OS) with the combination or monotherapy pooled across all major company-sponsored trials, as well as clinical factors associated with survival, in patients with immune checkpoint inhibitor (ICI) treatment-naïve unresectable/metastatic melanoma.METHODSData were pooled from six CheckMate studies in ICI treatment-naïve patients receiving NIVO + IPI (NIVO 1 mg/kg + IPI 3 mg/kg or NIVO 3 mg/kg + IPI 1 mg/kg) or NIVO monotherapy (3 mg/kg). OS was assessed for each treatment, as well as in select subgroups. Cox proportional multivariate analysis (MVA) and classification and regression tree (CART) analyses were performed within treatment arms.RESULTSMedian follow-up for OS was 45.0 months for patients treated with NIVO + IPI (n = 839) and 35.8 months for patients treated with NIVO (n = 536). OS was longer with NIVO + IPI versus NIVO monotherapy (hazard ratio, 0.78 [95% CI, 0.67 to 0.91]), with 6-year OS rates of 52% versus 41%, respectively. Consistent benefit was observed in BRAF-mutant and BRAF-wild-type patients and those with normal and elevated lactate dehydrogenase (LDH). Numerical difference in OS was also observed across PD-L1 expression levels, although more pronounced with no/low PD-L1 expression. Clinical factors associated with decreased survival in both the MVA and CART analyses were LDH > upper limit of normal with either treatment, age ≥65 years with NIVO + IPI, and the presence of liver metastases with NIVO monotherapy.CONCLUSIONIn this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.
UR - http://www.scopus.com/inward/record.url?scp=85209717917&partnerID=8YFLogxK
U2 - 10.1200/JCO.24.00400
DO - 10.1200/JCO.24.00400
M3 - Article
C2 - 39504507
AN - SCOPUS:85209717917
SN - 0732-183X
VL - 43
SP - 938
EP - 948
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -