TY - JOUR
T1 - 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)
AU - Hecht, J. Randolph
AU - Lonardi, Sara
AU - Bendell, Johanna
AU - Sim, Hao Wen
AU - Macarulla, Teresa
AU - Lopez, Charles D.
AU - van Cutsem, Eric
AU - Muñoz Martin, Andres J.
AU - Oh Park, Joon
AU - Greil, Richard
AU - Wang, Hong
AU - Hozak, Rebecca R.
AU - Gueorguieva, Ivelina
AU - Lin, Yong
AU - Rao, Sujata
AU - Ryoo, Baek Yeol
N1 - Funding Information:
J.R.H. received grants, personal fees, and nonfinancial support from ARMO BioSciences, a wholly owned subsidiary of Eli Lilly and Company, during the conduct of the study.
Publisher Copyright:
© 2021 by American Society of Clinical Oncology Creative Commons Attribution Non-Commercial No Derivatives 4.0 License
PY - 2021/4/1
Y1 - 2021/4/1
N2 - PURPOSE SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy with metastatic pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS SEQUOIA, a randomized, global phase III study, compared FOLFOX with PEG 1 FOLFOX as second line in gemcitabine-refractory PDAC. Patients were randomly assigned 1:1 (PEG 1 FOLFOX: FOLFOX) and stratified by prior gemcitabine and region. Eligible patients had only one prior gemcitabine-containing treatment. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), response evaluation per Response Evaluation Criteria in Solid Tumor (RECIST) 1.1, and safety. Exploratory analyses included biomarkers related to immune activation. RESULTS Between March 1, 2017, and September 9, 2019, 567 patients were randomly assigned PEG 1 FOLFOX (n 5 283) or FOLFOX (n 5 284). Most (94.7%) patients received prior gemcitabine plus nab paclitaxel. OS was similar comparing PEG 1 FOLFOX versus FOLFOX (median: 5.8 v 6.3 months; hazard ratio 5 1.045; 95% CI, 0.863 to 1.265). Also, PFS (median 2.1 v 2.1 months; hazard ratio 5 0.981; 95% CI, 0.808 to 1.190) and objective response rate (4.6% v 5.6%) were similar between the treatment arms. Most common ($ 35%) treatment-emergent adverse events in PEG 1 FOLFOX versus FOLFOX were thrombocytopenia (55% v 20%), anemia (40% v 16%), fatigue (61% v 45%), neutropenia (39% v 28%), abdominal pain (37% v 29%), nausea (45% v 41%), neuropathy (37% v 38%), and decreased appetite (35% v 31%). Exploratory analyses revealed increases in total IL-18, interferon (IFN)-g, and granzyme B and decreases in transforming growth factor (TGF)-b with the addition of PEG. CONCLUSION PEG added to FOLFOX did not improve efficacy in advanced gemcitabine-refractory PDAC. Safety findings were consistent as previously observed from PEG with chemotherapy; toxicity was manageable and tolerable. Exploratory pharmacodynamic results were consistent with immunostimulatory signals of the IL-10R pathway.
AB - PURPOSE SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy with metastatic pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS SEQUOIA, a randomized, global phase III study, compared FOLFOX with PEG 1 FOLFOX as second line in gemcitabine-refractory PDAC. Patients were randomly assigned 1:1 (PEG 1 FOLFOX: FOLFOX) and stratified by prior gemcitabine and region. Eligible patients had only one prior gemcitabine-containing treatment. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), response evaluation per Response Evaluation Criteria in Solid Tumor (RECIST) 1.1, and safety. Exploratory analyses included biomarkers related to immune activation. RESULTS Between March 1, 2017, and September 9, 2019, 567 patients were randomly assigned PEG 1 FOLFOX (n 5 283) or FOLFOX (n 5 284). Most (94.7%) patients received prior gemcitabine plus nab paclitaxel. OS was similar comparing PEG 1 FOLFOX versus FOLFOX (median: 5.8 v 6.3 months; hazard ratio 5 1.045; 95% CI, 0.863 to 1.265). Also, PFS (median 2.1 v 2.1 months; hazard ratio 5 0.981; 95% CI, 0.808 to 1.190) and objective response rate (4.6% v 5.6%) were similar between the treatment arms. Most common ($ 35%) treatment-emergent adverse events in PEG 1 FOLFOX versus FOLFOX were thrombocytopenia (55% v 20%), anemia (40% v 16%), fatigue (61% v 45%), neutropenia (39% v 28%), abdominal pain (37% v 29%), nausea (45% v 41%), neuropathy (37% v 38%), and decreased appetite (35% v 31%). Exploratory analyses revealed increases in total IL-18, interferon (IFN)-g, and granzyme B and decreases in transforming growth factor (TGF)-b with the addition of PEG. CONCLUSION PEG added to FOLFOX did not improve efficacy in advanced gemcitabine-refractory PDAC. Safety findings were consistent as previously observed from PEG with chemotherapy; toxicity was manageable and tolerable. Exploratory pharmacodynamic results were consistent with immunostimulatory signals of the IL-10R pathway.
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U2 - 10.1200/JCO.20.02232
DO - 10.1200/JCO.20.02232
M3 - Article
C2 - 33555926
AN - SCOPUS:85103683471
SN - 0732-183X
VL - 39
SP - 1108
EP - 1118
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -