Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
By S. Topalian, M. Sznol, D. McDermott, H. Kluger, R. Carvajal, W. Sharfman, J. Brahmer, D. Lawrence, M. Atkins, J. Powderly and 11 more. Journal of Clinical Oncology, 2023
1,526 citations recorded by the source corpus.
Purpose Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients and Methods Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Results Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Conclusion Overall survival following nivolumab treatment in patients with advanced treatment–refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/353d5ad31c8a810543f2960def65807480631d23
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
In Oncology
Citations in the corpus
- Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001 (2019, background): “Similarly, in the advanced melanoma cohort of patients from the dose-ranging phase I CA209-003 study, treatment with nivolumab resulted in a cumulative response rate of 28% [19] and 5year overall survival (OS) rate of 34% [20].”
- Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors (2015, neutral): “Hypothyroidism 0 0 0 1 (14) 1 (17) 2 (7)”
- Management of toxicities of immune checkpoint inhibitors. (2016, background): “Rates of AEs from nivolumab at 3 mg/kg and 10 mg/kg appear very similar [22,78].”