Treatment landscape of metastatic pancreatic cancer

• Published in: Cancer treatment reviews Vol. 96; p. 102180
• Main Authors: De Dosso, Sara, Siebenhüner, Alexander R., Winder, Thomas, Meisel, Alexander, Fritsch, Ralph, Astaras, Christoforos, Szturz, Petr, Borner, Markus
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.2021
• Subjects: Albumins - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - surgery; Clinical Trials, Phase III as Topic; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Fluorouracil - administration & dosage; FOLFIRINOX; Gemcitabine; Humans; Irinotecan - administration & dosage; Leucovorin - administration & dosage; Liposomal-irinotecan; Liposomes - administration & dosage; Nab-paclitaxel; Neoplasm Metastasis; Oxaliplatin - administration & dosage; Paclitaxel - administration & dosage; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Precision medicine; Randomized Controlled Trials as Topic; FOLFIRINOX; Liposomal-irinotecan; Precision medicine; Gemcitabine; Pancreatic cancer; Biomarkers; Nab-paclitaxel
• ISSN: 0305-7372; 1532-1967
• DOI: 10.1016/j.ctrv.2021.102180

•Survival outcomes for patients with pancreatic cancer remain poor.•FOLFIRINOX and gemcitabine plus nab-paclitaxel are the treatments of choice for patients who are not surgical candidates; both combinations have shown a survival advantage over previously standard gemcitabine monotherapy.•Second-line therapies, especially nanoliposomal irinotecan plus 5 fluorouracil–folinic acid, might prolong survival after first-line gemcitabine failure.•Beyond the standard of care, there is a lack of molecular and genetic biomarkers for optimal stratification of patients and in guiding treatment decisions.•Focusing clinical trial designs on molecular screening of patients will be crucial, and drug combination strategy seems the most interesting approach. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with a dismal prognosis. The lack of symptoms in the early phase of the disease makes early diagnosis challenging, and about 80–85% of the patients are diagnosed only after the disease is locally advanced or metastatic. The current front-line treatment landscape in local stages comprises surgical resection and adjuvant chemotherapy. In Switzerland, although both FOLFIRINOX and gemcitabine plus nab-paclitaxel regimens are feasible and comparable in the first-line setting, FOLFIRINOX is preferred in the treatment of fit (Eastern Cooperative Oncology Group [ECOG] performance status [PS]: 0–1), young (<65 years old) patients with few comorbidities and normal liver function, while gemcitabine plus nab-paclitaxel is used to treat less fit (ECOG PS: 1–2) and more vulnerable patients. In the second-line setting of advanced PDAC, there is currently only one approved regimen, based on the phase III NAPOLI-1 trial. Furthermore, the use of liposomal-irinotecan in the second line is supported by real-world data. Beyond the standard of care, various alternative treatment modalities are being explored in clinical studies. Immunotherapy has demonstrated only limited benefits until now, and only in cases of high microsatellite instability (MSI-H). However, data on the benefit of poly (ADP-ribose) polymerase (PARP) inhibition as maintenance therapy in patients with germline BRCA-mutated tumors might signal of an advance in targeted therapy. Currently, there is a lack of molecular and genetic biomarkers for optimal stratification of patients and in guiding treatment decisions. Thus, identification of predictive and prognostic biomarkers and evaluating novel treatment strategies are equally relevant for improving the prognosis of metastatic pancreatic cancer patients.