Addition of Tocilizumab to First-Line Gemcitabine Plus Nab-Paclitaxel for Patients With Advanced Pancreatic Cancer
According to results from the phase 2 PACTO study, the addition of tocilizumab, a humanized anti-IL6R antibody, to first-line gemcitabine plus nab-paclitaxel did not significantly improve clinical outcomes among patients with advanced pancreatic cancer. However, the addition of the IL6R inhibition may mitigate cachexia.
Tocilizumab “inhibits IL-6 signaling by blocking its binding to both soluble and membrane-resident IL-6R, JAK/STAT3 pathway activation and subsequent inflammation,” stated Inna Chen, MD, Copenhagen University Hospital—Herlev and Gentofte, Herlev, Denmark, and coauthors. “In a phase I study… combining [tocilizumab with gemcitabine plus nab-paclitaxel]-rechallenge achieved an 80% disease control rate and tumor shrinkage.”
In this open-label study, 141 treatment-naïve patients with locally advanced or metastatic pancreatic cancer were randomized on a 1-to-1 basis to receive 1000 mg/m2 of gemcitabine plus 125 mg/m2 of nab-paclitaxel either with (tocilizumab arm, n = 70) or without (chemotherapy alone arm, n = 71) 8 mg/kg of tocilizumab in 28-day cycles until disease progression or unacceptable toxicity. The primary end point was 6-month overall survival (OS) rate. Key secondary end points included progression-free survival (PFS), overall response rate (ORR), and safety. An exploratory end point was cachexia.
At a median follow-up of 8.1 months, the 6-month OS rate was 68.6% in the tocilizumab arm and 62% in the chemotherapy alone arm (P = .409). The 18-month OS rates were 27.1% and 7% (P = .001), respectively. Median OS was 8.4 months in the tocilizumab arm and 8 months in the chemotherapy alone arm (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.54 to 1.05; P = .096), and the median PFS was 5.6 months and 5.5 months, respectively (HR 0.85; 95% CI, 0.60 to 1.19; P = .339). The ORR was 37.1% in the tocilizumab arm and 35.2% in the chemotherapy alone arm. Grade ≥3 treatment-related adverse events occurred in 88.1% of patients in the tocilizumab arm and 63.4% of patients in the chemotherapy alone arm (P < .001). Two treatment-related deaths occurred in the tocilizumab arm.
The 2-month median change in muscle loss was +0.1013% in the tocilizumab arm and -3.430% in the chemotherapy alone arm (P = .0012). The 4-month median change in muscle loss was + 0.7044% in the tocilizumab arm and -3.353% in the chemotherapy alone arm (P = .036). The 2-month incidence of muscle loss was 43.48% in the tocilizumab arm and 73.52% in the chemotherapy alone arm (P = .0045) and the 4-month incidence of muscle loss was 41.82% and 68.75% (P = .0062), respectively.
“Although the primary end point 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,” concluded Dr Chen et al.
“The topic of mitigating cachexia is a highly topical one,” added Journal of Clinical Oncology associate editor Eileen O’Reilly, MD, Memorial Sloan Kettering Cancer Center, New York, New York. “This randomized phase II study, albeit negative for primary end point, provides some insights for the field and an avenue for further investigation.”
Source:
Chen IM, Johansen JS, Theile S, et al. Randomized phase II study of nab-paclitaxel and gemcitabine with or without tocilizumab as first-line treatment in advanced pancreatic cancer: Survival and cachexia. J Clin Oncol. Published online: May 12, 2025. doi: 10.1200/JCO.23.01965
