The approved doses of the single agent nivolumab - an anti-programmed cell death protein 1 (PD-1) monoclonal antibody - for renal cell carcinoma (RCC) are 3 mg/kg and a 240-mg flat dose, despite efficacy shown at lower doses in earlier CheckMate trials.
In view of financial constraints, the minimum dose of nivolumab required for efficacy remains a critical area of inquiry.
A retrospective review of RCC patients receiving single-agent anti-PD-1 treatment was conducted. Using the median cutoff of the maximum dose per body weight received, we investigated the effect of lower dosages on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse event-free survival (irAE-FS). Survival analysis was made by Kaplan-Meier, by uni- and multivariable Cox models, and by modeling the statistical interaction between dosages and survival.
32 patients were recruited: 8 patients (25%) receiving first-line treatment and 24 (75%) receiving second-line treatment and beyond. A median split at 2.15 mg/kg yielded 16 patients in both the lower-dose (LD) and the higher-dose (HD) cohort. Hazard ratios (HRs) demonstrated no difference in OS after adjustment for gender (HR = 0.22, 95% CI 0.05-1.05, p = 0.054; favoring LD), as well as in PFS after adjustment for gender and concurrent radiation therapy (HR = 0.58, 95% CI 0.25-1.34, p = 0.210; favoring LD). No differences in ORR were observed (50.0 vs. 43.8%, p = 1.00, in the LD and the HD cohort, respectively). Immune-related phenomena were observed in the LD group, including pseudoprogression and increased all-grade immune-related toxicities (irAE-FS: HR = 1.72, 95% CI 0.48-6.14, p = 0.293; favoring HD). Iterative dichotomization of dosages showed no dose-OS or dose-irAE-FS relationship.
Our study suggests no apparent reduction in efficacy when using a low-dosage nivolumab regimen.
Oncology. 2021 Jan 13 [Epub ahead of print]
Joseph J Zhao, Nesaretnam Barr Kumarakulasinghe, Vaishnavi Muthu, Matilda Lee, Robert Walsh, Jia Li Low, Joan Choo, Hon Lyn Tan, Wan Qin Chong, Yvonne Ang, Gloria Chan, Wei Peng Yong, Yiqing Huang, Natalie Ngoi, Alvin Wong
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, ., Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/33440374