In a phase II trial reported in the Journal of Clinical Oncology, Chen et al attempted to determine whether there is a benefit to adding tocilizumab to nab-paclitaxel and gemcitabine in the first-line treatment of patients with advanced pancreatic cancer.
Study Details
In the open-label trial, 141 patients from one center in Denmark and one in Norway were randomly assigned between January 2017 and July 2021 to receive gemcitabine at 1,000 mg/m2 and nab-paclitaxel at 125 mg/m2 on days 1, 8, and 15 with (n = 70) or without (n = 71) tocilizumab at 8 mg/kg on day 1 once every 4 weeks. The primary outcome measure was overall survival at 6 months. Cachexia was an exploratory outcome, with assessment of relation to cachexia-promoting protein growth differentiation factor 15 (GDF15).
Key Findings
Overall survival at 6 months was 68.6% (95% confidence interval [CI] = 56.3%–78.1%) in the tocilizumab group vs 62.0% (95% CI = 49.6%–72.1%) in the control group (P = .409). At 18 months, overall survival was 27.1% vs 7.0% (P = .001). No differences in median overall survival (8.4 vs 8.0 months, P = .096), median progression-free survival (5.6 vs 5.5 months, P = .339), or objective response rate (37.1% vs 35.2%) were observed.
Grade ≥ 3 treatment-related adverse events occurred in 88.1% of the tocilizumab group vs 63.4% of the control group (P < .001). The tocilizumab group exhibited decreased muscle loss vs the control group, with median changes of 10.1013% vs –3.430% (P = .0012) at 2 months and 10.7044% vs –3.353% (P = .036) at 4 months. The incidence of muscle loss was 43.5% vs 73.5% (P = .0045) at 2 months and 41.2% vs 68.8% (P = .0062) at 4 months. GDF15 levels were not altered in either group.
The investigators concluded: “Although the primary endpoint was not met and [treatment-related adverse events] were increased by [tocilizumab], increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.”
Inna M. Chen, MD, of the Department of Oncology, Copenhagen University Hospital–Herlev and Gentofte, Herlev, Denmark, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was funded by Celgene/Bristol Myers Squibb and others. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
