Systemic therapy in metastatic pancreatic adenocarcinoma: current practice and perspectives

Lellouche, Lisa; Dermine, Solène; Brézault, Catherine; Chaussade, Stanislas

doi:10.1177/17588359211018539

Cited by 11 publications

(9 citation statements)

References 125 publications

(174 reference statements)

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“…He had both BRCA2 mutation and PD-L1 expression, and he was started on pembrolizumab and olaparib. Olaparib, a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor improved median progress-free survival in patients with germline BRCA1 or BRCA2 mutations, who were not progressing after at least 16 weeks of first-line platinum-based chemotherapy [ 9 ]. In one of the recent reports, a patient with BRCA1 mutation and high tumor mutation burden showed complete response to olaparib and pembrolizumab combination therapy [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Survival Benefit of Pembrolizumab for Patients With Pancreatic Adenocarcinoma: A Case Series

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with 5-year survival rate of 10%. Evidence about pembrolizumab usage for PDAC is limited even though it is Food and Drug Administration (FDA)-approved for treatment of advanced pancreatic cancer with deficient mismatch repair expression (dMMR) or high tumor mutational burden (TMB) where as there is limited evidence for programmed death-ligand 1 (PD-L1)-positive PDACs. We present three patients with different stages of advanced PDAC treated with pembrolizumab as single maintenance therapy or combination with other therapy. Case 1 is a patient with borderline resectable PDAC, treated with neoadjuvant chemotherapy and surgical resection, followed with pembrolizumab as maintenance therapy with no progression for 4 years after test showed patient was dMMR positive. Case 2 is a patient who was found to have locally advanced PDAC, treated with neoadjuvant chemotherapy and surgical resection followed by multiple line of treatment with programmed cell death-1 ( PD-1 ) and breast cancer gene 2 ( BRCA2 )-positive status treated with pembrolizumab and olaparib maintenance without any evidence of progression for more than 3 years. Case 3 is a patient with metastatic PDAC with PD-1 and BRCA2 -positive status initially treated with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) and gemcitabine plus nab-paclitaxel switched to irinotecan liposomal, at the same time was started on maintenance pembrolizumab and olaparib with no progression on computed tomography (CT) surveillance for 8 months. For patient with different stages of PDAC with dMMR mutation or PD-1 expression, pembrolizumab should be explored more as maintenance therapy for patients with surgical operable PDAC to decrease recurrence, or as a combination with targeted therapy or chemotherapy to prolong survival in patients with advanced PDAC.

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Section: Discussionmentioning

confidence: 99%

Survival Benefit of Pembrolizumab for Patients With Pancreatic Adenocarcinoma: A Case Series

et al. 2022

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“…FOLFIRINOX is the most popular regimen if the patient’s status is good enough, but the differences in the effects and safety of these various regimens remains controversial. 9 , 10 …”

Section: Discussionmentioning

confidence: 99%

“…FOLFIRINOX is the most popular regimen if the patient's status is good enough, but the differences in the effects and safety of these various regimens remains controversial. 9,10 This current meta-analysis analysed six studies that enrolled 858 patients to evaluate the effects and safety of FOLFIRINOX compared with FOLFIRI, FOLFOX and S-1 as second-line regimens after failure of gemcitabine-based chemotherapy in advanced pancreatic cancer. Compared with patients treated with the other three regimens, patients treated with FOLFIRINOX had a significantly higher PFS, OS, ORR and DCR.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 For patients that accept gemcitabinebased first-line chemotherapy, the subsequent recommended regimens are those combinations that contain 5-FU or capecitabine, including FOLFIRINOX, FOLFOX (FOL -folinic acid, F -fluorouracil , OX -oxaliplatin), FOLFIRI (FOL -folinic acid, F -fluorouracil , IRI -irinotecan), CAPOX (CAP -capecitabine, OX -oxaliplatin) or a single use of 5-FU and capecitabine infusions. [9][10][11] Single use of tegafur (S-1) and combination regimens containing S-1 are also widely used in Asian countries for patients with pancreatic cancer as subsequent therapy after gemcitabine-based chemotherapy. 12 The choice to use these regimens is usually based on the status of the patient and experience of the physicians.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy: A systematic review and meta-analysis

Wang

et al. 2022

J Int Med Res

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Objective To undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN [irinotecan], OX [oxaliplatin]) after failure of gemcitabine-based first-line therapy in patients with pancreatic cancer. Methods This meta-analysis searched electronic databases, including Embase®, Medline, PubMed® and the Cochrane library, for eligible studies that reported the use of FOLFIRINOX and other drug regimens as second-line chemotherapy after failure of gemcitabine-based chemotherapy. Pooled analyses for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and grade 3/4 treatment-emergent adverse events (TRAEs) were undertaken. Results The analysis included six studies with a total of 858 patients. Compared with the three other second-line regimens, FOLFIRINOX had a significantly longer PFS (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52, 0.89) and OS (HR 0.71, 95% CI 0.59, 0.86); and a significantly better ORR (HR 0.43, 95% CI 0.23, 0.80) and DCR (HR 0.71, 95% CI 0.58, 0.88). However, grade 3/4 adverse events were more frequently reported in patients administered FOLFIRINOX compared with the other three regimens. Conclusion FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy. Research Registry number: reviewregistry1300

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“…Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with an extremely poor prognosis and high mortality (less than 10% 5-year survival) and will be the third major cause of cancer-related deaths [ 1 , 2 ]. Because of lacking early symptoms and effective detection methods, most patients(80%–85%) present with locally advanced or distant metastatic disease that cannot be resected [ 3 , 4 ]. First-line treatment of metastatic pancreatic cancer is currently only effective in combination with chemotherapy with cytotoxic agents [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

A Potential Prognostic Marker PRDM1 in Pancreatic Adenocarcinoma

Zhou

Zhang

Zhu

et al. 2022

Journal of Oncology

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Pancreatic adenocarcinoma (PAAD) is a major threat to people’s health. PRDM1 is a transcription factor with multiple functions, and its functions have been validated in a variety of tumors; however, there are few studies reported on PRDM1 in PAAD. Using the GEPIA2 database, this research found that PRDM1 expression in PAAD was significantly higher than that in normal pancreatic tissue. The Kaplan-Meier Plotter database showed that high expression of PRDM1 in PAAD has a poor prognosis, suggesting that PRDM1 may be a potential prognostic marker in PAAD. The cBioPortal database shows that the expression of PRDM1 in PAAD is significantly correlated with its methylation degree. Further analysis on the coexpressed genes of PRDM1 in PAAD was performed by using LinkedOmics database to explore potential mechanisms. Based on gene enrichment analysis, PRDM1 was implicated in many pathways involved in tumor progression. In the construction of a PPI network of PRDM1 and its coexpressed gene protein via the STRING database, we found that PRDM1 may be involved in the pathogenesis and development of PAAD. TIMER database suggested that a high level of PRDM1 has a significant positive correlation with macrophages, neutrophils, and DCs. Potential methylation sites of PRDM1 were found through DNMIVD database, and MethSurv database explored eight sites which were significantly related with the prognosis of PAAD. In conclusion, PRDM1 may work as a prognostic marker or even provide a potential therapeutic strategy in PAAD.

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Systemic therapy in metastatic pancreatic adenocarcinoma: current practice and perspectives

Cited by 11 publications

References 125 publications

Survival Benefit of Pembrolizumab for Patients With Pancreatic Adenocarcinoma: A Case Series

Survival Benefit of Pembrolizumab for Patients With Pancreatic Adenocarcinoma: A Case Series

Efficacy and safety of FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy: A systematic review and meta-analysis

A Potential Prognostic Marker PRDM1 in Pancreatic Adenocarcinoma

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