Pegilodecakin plus leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) did not improve overall survival, progression-free survival, or overall response rate compared with FOLFOX alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who experienced disease progression on first-line gemcitabine therapy, according the results of the phase 3 SEQUOIA study. The data were published in the Journal of Clinical Oncology.

Early studies suggested that pegilodecakin, a pegylated recombinant human interleukin (IL)-10, might have clinical activity against PDAC and other solid tumors when combined with FOLFOX. The aim of this trial was to evaluate the safety and efficacy of this combination as a second-line therapy in patients with gemcitabine-refractory PDAC.

SEQUOIA investigators randomly assigned 567 patients with PDAC to receive either pegilodecakin plus FOLFOX (n=283) or FOLFOX alone (n=284). The primary end point was OS. Secondary end points included PFS, duration of response (DOR), and safety.

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At baseline, the median patient age was 65 years. Carbohydrate antigen (CA) 19-9 was greater than 59 the upper limit of normal (ULN) among 41.4% of patients, greater than normal but less than 59 ULN among 43.6%, and normal among 15.0%.

The addition of pegilodecakin to FOLFOX resulted in a median OS similar to what was seen with FOLFOX alone. The median OS was 5.8 months with the combination compared with 6.3 months with FOLFOX (HR, 1.045; 95% CI, 0.863-1.265). The median PFS was 2.1 months in both arms (HR, 0.981; 95% CI, 0.808-1.190).

The ORR was also comparable, at 4.6% with pegilodecakin plus FOLFOX and 5.6% with FOLFOX alone. The disease control rate was 42.8% and 36.6% with the combination and FOLFOX, respectively. The DOR was also found to be similar (combination, 5.0 months vs FOLFOX, 5.2 months).

Common treatment-emergent adverse events that occurred more frequently with the pegilodecakin-containing approach included thrombocytopenia, anemia, fatigue, neutropenia, and abdominal pain. A total of 25.9% of patients required pegilodecakin dose modification due to adverse events; 48.6% required a dose delay.

“Stimulating the IL-10 pathway in combination with FOLFOX did not benefit second-line pancreatic cancer in this patient population,” the study authors concluded.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.


Hecht JR, Lonardi S, Bendell J, et al. Randomized phase III study of FOLFOX alone or with pegilodecakin as second-line therapy in patients with metastatic pancreatic cancer that progressed after gemcitabine (SEQUOIA). J Clin Oncol. Published online February 8, 2021. doi:10.1200/JCO.20.02232