Adding pegylated IL-10 to second-line FOLFOX does not improve OS in advanced pancreatic cancer

Adding pegilodecakin, a pegylated form of interleukin-10 (IL-10), to second-line FOLFOX chemotherapy does not significantly improve overall survival (OS) or other outcomes in patients with advanced pancreatic ductal adenocarcinoma (PDAC) as compared with FOLFOX alone, results of the phase III SEQUOIA trial have shown.

 

Despite promising activity shown in the phase I IVY trial in patients with gemcitabine-refractory PDAC, the recently reported phase III SEQUOIA trial showed similar OS, progression-free survival (PFS) and objective response rate (ORR) with pegilodecakin plus FOLFOX vs FOLFOX alone in the same population of patients (n=567). [Curr Oncol Rep 2019;21:19; Hecht JR, et al, ASCO GI 2020, abstract 637]

 

Among the 567 patients who were randomized 1:1 to receive 12 cycles of FOLFOX (leucovorin 400 mg/m², oxaliplatin 85 mg/m², 5-FU 400 mg/m² bolus and x2,400 mg/m² infusion over 46–48 hours) with or without pegilodecakin (0.4 mg/day if ≤80 kg, 0.8 mg/day if >80 kg), 94.7 percent had received first-line treatment with gemcitabine plus nab-paclitaxel.

 

OS, the primary endpoint, was at a median of 5.78 months in the pegilodecakin plus FOLFOX group vs 6.28 months in the FOLFOX group (hazard ratio [HR], 1.045; 95 percent confidence interval [CI], 0.863 to 1.265; p=0.6565).

 

Median PFS was 2.14 months for pegilodecakin plus FOLFOX vs 2.10 months for FOLFOX alone (HR, 0.981; 95 percent CI, 0.808 to 1.190; p=0.8144).

 

“The ORR, disease control rate, median duration of response, and median time to response were all very closely matched for the respective arms, at 4.6 percent vs 5.6 percent, 42.8 percent vs 36.6 percent, 5.0 months vs 5.2 months, and 1.9 months vs 1.9 months, respectively,” reported investigator Dr Johanna C. Bendell of Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee, US.

 

In the SEQUOIA trial, grade ≥3 adverse events that were 5 percent more common in patients receiving pegilodecakin plus FOLFOX vs FOLFOX alone included thrombocytopenia (25.2 percent vs 3.6 percent), anaemia (16.2 percent vs 4.0 percent), neutropenia (29.5 percent vs 22.7 percent), and fatigue (17.6 percent vs 10.8 percent).

 

“The safety findings were consistent with previous data of pegilodecakin plus chemotherapy,” said Bendell. “The toxicities were manageable and tolerable.”

 

Pegilodecakin was hypothesized to help overcome the immunosuppressive PDAC microenvironment, particularly when combined with chemotherapy, due to its extended half-life that enables better stimulation of CD8⁺ T cells and reversal of T-cell exhaustion. [Cancer Cell 2018;34:775-791]

 

“To me, [SEQUOIA] is a leap of faith. We have some early efficacy results, but is that enough, particularly when the phase I data reflect only 21 patients?” commented discussant Dr Andrea Wang-Gillam of Washington University in St Louis, Missouri, US. “We need some robust phase II data with go or no-go signals before jumping into phase III.”

 

“We are currently exploring cytokine levels and T-cell receptor clonality to determine if these biomarkers lend insight into the mechanisms of disease resistance,” said Bendell. “There are no further plans to pursue pegilodecakin development in PDAC, given the SEQUOIA findings.”