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Checkpoint inhibitors in pancreatic cancer
Andreas Henriksen1, Anne Dyhl-Polk1, Inna Chen1
1Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Introduction:
Immune checkpoint inhibitors, targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways have shown remarkable potential in several types of cancer. In this review we summarize published and ongoing studies on checkpoint inhibitors in pancreatic cancer (PC).
Methods:
We conducted a systematic literature search using Medline and Embase up to November 2018; additional data from a search on clinicaltrials.gov were included. Endpoints of interest encompassed overall survival (OS), progression free survival (PFS) and response rates.
Results:
Full-length articles constituted a minority of included records. Furthermore, few patients were enrolled, and only few phase II studies were identified. Disappointing limited activity was demonstrated with single-agent checkpoint inhibitors in PC. A small number of studies on combination therapy showed promise with regards to response. But overall, PC patients treated with checkpoint inhibitors were not shown to elicit improvement in response rates or overall survival.
Conclusion:
Checkpoint inhibition monotherapy has failed to elicit efficacy in patients with pancreatic cancer. Combination regimens including chemotherapy have shown initial promise, but these results need to be verified. Numerous studies on checkpoint inhibition in PC are ongoing.
Insights
Immune checkpoint inhibitors targeting CTLA-4 and PD-1/PD-L1 pathways show limited efficacy as monotherapy for pancreatic cancer (PC). Combination therapies offer potential but require further investigation.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1/PD-L1 pathways have revolutionized cancer treatment.
- Their efficacy in pancreatic cancer (PC) remains under investigation.
Purpose of the Study:
- To review published and ongoing studies on ICI efficacy in pancreatic cancer.
- To evaluate outcomes such as overall survival, progression-free survival, and response rates.
Main Methods:
- Systematic literature search of Medline and Embase up to November 2018.
- Inclusion of data from clinicaltrials.gov.
- Analysis of endpoints including overall survival, progression-free survival, and response rates.
Main Results:
- Limited activity observed with single-agent ICIs in pancreatic cancer.
- Few studies identified, with small patient enrollment and predominantly Phase II trials.
- Combination therapies showed some promise for response, but overall survival and response rates did not improve.
Conclusions:
- Monotherapy with checkpoint inhibitors has failed to demonstrate efficacy in pancreatic cancer.
- Combination regimens, particularly with chemotherapy, show initial promise but require validation.
- Numerous ongoing studies are investigating checkpoint inhibition in pancreatic cancer.
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