Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward
Abstract
:1. Introduction
2. Methods
3. Molecular Subtypes
4. Mainstay (First, Second Line, and Biomarker Driven Treatments)
4.1. First-Line Treatments
4.2. Second-Line Treatments
4.3. Biomarker-Driven Treatments
5. Maintenance Therapy
Authors/Study Title | Study Design | Population | Criteria for Starting Maintenance | Maintenance Strategy | mPFS | mOS | Prevalence of (Selected) Side Effects |
---|---|---|---|---|---|---|---|
Golan et al. 2019 [43] POLO trial | Prospective phase 3 trial, placebo-controlled, randomized 3:2 | 154 patients with metastatic PDAC and germline BRCA1 or BRCA2 mutation | No progressive disease after 4 months first-line platinum-based chemotherapy | Olaparib | Olaparib/placebo 7.4 vs. 3.8 months | Olaparib/placebo 18.9 vs. 18.1 months (interim analysis at a data maturity of 46%) | Serious adverse events ≥ 3° olaparib/placebo 40% vs. 23%, most common serious adverse events were anemia (11%), fatigue, or asthenia (5%) and decreased appetite (3%) |
Dahan et al. 2018 [39] PRODIGE 35/PANOPTIMOX trial | Prospective phase 2 trial, randomized to 3 arms, arm A: FOLFIRINOX over 6 months, arm B: 8 cycles FOLFIRINOX followed by 5-FU/leucovorin maintenance therapy, arm C: alternating gemcitabine and FOLFIRI every 2 months | 273 patients with metastatic PDAC | No progressive disease after 8 cycles FOLFIRINOX | 5-FU/leucovorin | Arm A/arm B 6.3 vs. 5.7 months (arm C: 4.5 months) | Arm A/arm B 10.1 vs. 11.2 months (arm C: 7.3 months) | Neurotoxicity ≥3° arm A/arm B 10% vs. 19% (reescalation to FOLFIRINOX, higher cumulative oxaliplatin dose) |
Petrioli et al. 2020 [41] | Observational prospective | 31 patients with metastatic or locally advanced PDAC | No progressive disease after GA for ≤3 cycles (3 months) | Gemcitabine | 6.4 months | 13.4 months | Hematological toxicity 3° (19%) |
Reure et al. 2016 [40] | Retrospective | 30 patients with metastatic PDAC | No progressive disease after 4 to 8 cycles of FOLFIRINOX | Capecitabine | 5 months (on capecitabine maintenance) | 17 months | Hand-foot syndrome ≥ 3° (16.6%) |
Franck et al. 2019 [38] | Retrospective | 22 patients with metastatic or locally advanced PDAC | No progressive disease after FOLFIRINOX for a median of 4 months (5–12 cycles) | FOLFIRI | 8 months | 46 months (low data maturity) | Neutropenia and anemia ≥ 3° in both 14% of the patients |
6. Surgery
7. Treatment Options in Elderly Patients
8. Staging
9. Supportive Therapy
9.1. Pancreatic Enzyme Replacement
9.2. Small Bacterial Overgrowth
9.3. Prophylaxis of Thromboembolism
9.4. Improving Care in Patients with PDAC
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Subtype | Characteristics | Incidence | Survival (Months) |
---|---|---|---|
Squamous | Enriched for activated α6β1 and α6β4 integrin signaling and activated EGF signaling. Hypermethylation of genes that govern pancreatic endodermal cell-fate determination leading to a complete loss of endodermal identity. | 31% | 13.3 |
Aberrantly differentiated endocrine exocrine (ADEX) | Transcriptional networks in later stages of pancreatic development and differentiation. Transcription factors NR5A2, MIST1 important in acinar cell differentiation and pancreatitis regeneration. Genes associated with endocrine differentiation and MODY. | 19% | 25.6 |
Pancreatic progenitor | Pancreas development, gene programs regulating fatty acid oxidation, steroid hormone biosynthesis, drug metabolism, and O-linked glycosylation of mucins. | 29% | 23.7 |
Immunogenic | Immune infiltrate, B cell signaling pathways, antigen presentation, CD4+ T cell, CD8+ T cell, and Toll-like receptor signaling pathways. | 21% | 30 |
Regimen | Oxaliplatin * | Leucovorin * | Irinotecan # | Fluorouracil a | Fluorouracil b | Selected Adverse Events ≥ 3° |
---|---|---|---|---|---|---|
FOLFIRINOX [19] | 85 mg/m2 | 400 mg/m2 | 180 mg/m2 | 400 mg/m2 | 2.400 mg/m2 | Sensory neuropathy 9.3%, fatigue 23.6%, neutropenia 45,7% (filgrastim was administered in 43% of the patients), vomiting 14.5%, diarrhea 12.7% |
mFOLFIRINOX [23] | 85 mg/m2 | 400 mg/m2 | 180 mg/m2 (after the enrollment of 162 of 493 patients, the dose of irinotecan was reduced to 150 mg/m2) | No fluorouracil bolus was administered | 2.400 mg/m2 | Sensory neuropathy 9.0%, fatigue 11.0%, neutropenia 28.4% (filgrastim was administered in 62% of the patients), vomiting 5.1%, diarrhea 18,6% (20.0% who received irinotecan at a dose of more than 175 mg/m2 and 17.1% who received a dose of 150 mg/m2) |
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Franck, C.; Müller, C.; Rosania, R.; Croner, R.S.; Pech, M.; Venerito, M. Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward. Cancers 2020, 12, 1955. https://doi.org/10.3390/cancers12071955
Franck C, Müller C, Rosania R, Croner RS, Pech M, Venerito M. Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward. Cancers. 2020; 12(7):1955. https://doi.org/10.3390/cancers12071955
Chicago/Turabian StyleFranck, Caspar, Christian Müller, Rosa Rosania, Roland S. Croner, Maciej Pech, and Marino Venerito. 2020. "Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward" Cancers 12, no. 7: 1955. https://doi.org/10.3390/cancers12071955
APA StyleFranck, C., Müller, C., Rosania, R., Croner, R. S., Pech, M., & Venerito, M. (2020). Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward. Cancers, 12(7), 1955. https://doi.org/10.3390/cancers12071955