TY - JOUR
T1 - Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer
T2 - A Phase Ib Study
AU - Kamath, Suneel D.
AU - Kalyan, Aparna
AU - Kircher, Sheetal
AU - Nimeiri, Halla
AU - Fought, Angela J.
AU - Benson, Al
AU - Mulcahy, Mary
N1 - Funding Information:
The study drug was provided with support from Bristol-Myers Squibb.
Publisher Copyright:
© AlphaMed Press 2019
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background: Pancreatic ductal adenocarcinoma (PDAC) remains resistant to chemotherapy and immunotherapy individually because of its desmoplastic stroma and immunosuppressive tumor microenvironment. Synergizing cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint blockade with chemotherapy could overcome these barriers. Here we present results of a phase Ib trial combining ipilimumab and gemcitabine in advanced PDAC. Materials and Methods: This was a single-institution study with a 3 + 3 dose-escalation design. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included determining the toxicity profile, objective response rate (ORR), median progression-free survival (PFS), and overall survival (OS). Results: Twenty-one patients were enrolled, 13 during dose escalation and 8 at the MTD. The median age was 66 years, 62% were female, 95% had stage IV disease, and 67% had received at least one prior line of therapy. The primary objective to establish the MTD was achieved at doses of ipilimumab 3 mg/kg and gemcitabine 1,000 mg/m2. The most common grade 3 or 4 adverse events were anemia (48%), leukopenia (48%), and neutropenia (43%). The ORR was 14% (3/21), and seven patients had stable disease. Median response duration for the three responders was 11 months, with one response duration of 19.8 months. Median PFS was 2.78 months (95% confidence interval [CI], 1.61–4.83 months), and median OS was 6.90 months (95% CI, 2.63–9.57 months). Conclusion: Gemcitabine and ipilimumab is a safe and tolerable regimen for PDAC with a similar response rate to gemcitabine alone. As in other immunotherapy trials, responses were relatively durable in this study. Implications for Practice: Gemcitabine and ipilimumab is a safe and feasible regimen for treating advanced pancreatic cancer. Although one patient in this study had a relatively durable response of nearly 20 months, adding ipilimumab to gemcitabine does not appear to be more effective than gemcitabine alone in advanced pancreatic cancer.
AB - Background: Pancreatic ductal adenocarcinoma (PDAC) remains resistant to chemotherapy and immunotherapy individually because of its desmoplastic stroma and immunosuppressive tumor microenvironment. Synergizing cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint blockade with chemotherapy could overcome these barriers. Here we present results of a phase Ib trial combining ipilimumab and gemcitabine in advanced PDAC. Materials and Methods: This was a single-institution study with a 3 + 3 dose-escalation design. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included determining the toxicity profile, objective response rate (ORR), median progression-free survival (PFS), and overall survival (OS). Results: Twenty-one patients were enrolled, 13 during dose escalation and 8 at the MTD. The median age was 66 years, 62% were female, 95% had stage IV disease, and 67% had received at least one prior line of therapy. The primary objective to establish the MTD was achieved at doses of ipilimumab 3 mg/kg and gemcitabine 1,000 mg/m2. The most common grade 3 or 4 adverse events were anemia (48%), leukopenia (48%), and neutropenia (43%). The ORR was 14% (3/21), and seven patients had stable disease. Median response duration for the three responders was 11 months, with one response duration of 19.8 months. Median PFS was 2.78 months (95% confidence interval [CI], 1.61–4.83 months), and median OS was 6.90 months (95% CI, 2.63–9.57 months). Conclusion: Gemcitabine and ipilimumab is a safe and tolerable regimen for PDAC with a similar response rate to gemcitabine alone. As in other immunotherapy trials, responses were relatively durable in this study. Implications for Practice: Gemcitabine and ipilimumab is a safe and feasible regimen for treating advanced pancreatic cancer. Although one patient in this study had a relatively durable response of nearly 20 months, adding ipilimumab to gemcitabine does not appear to be more effective than gemcitabine alone in advanced pancreatic cancer.
KW - Gemcitabine
KW - Immune checkpoint inhibition
KW - Immunotherapy
KW - Ipilimumab
KW - Pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=85075316959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85075316959&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2019-0473
DO - 10.1634/theoncologist.2019-0473
M3 - Article
C2 - 31740568
AN - SCOPUS:85075316959
SN - 1083-7159
VL - 25
SP - e808-e815
JO - Oncologist
JF - Oncologist
IS - 5
ER -
