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.

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%.


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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.

Reference

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