Second-line treatment options for patients with metastatic pancreatic ductal adenocarcinoma: A systematic literature review

• Published in: Cancer treatment reviews Vol. 113; p. 102502
• Main Authors: Dayyani, Farshid, Macarulla, Teresa, Johnson, Andrew, Wainberg, Zev A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2023
• Subjects: Adenocarcinoma - drug therapy; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - pathology; Fluorouracil; Humans; Irinotecan; Leucovorin - therapeutic use; Pancreatic adenocarcinoma; Pancreatic cancer; Pancreatic ductal adenocarcinoma (PDAC); Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Prospective Studies; Second-line treatment; Systematic literature review; Second-line treatment; Pancreatic adenocarcinoma; Pancreatic ductal adenocarcinoma (PDAC); Pancreatic cancer; Systematic literature review
• ISSN: 0305-7372; 1532-1967
• DOI: 10.1016/j.ctrv.2022.102502

•This review characterizes the treatment landscape for 2L metastatic PDAC.•Liposomal irinotecan + 5-FU/LV is the only 2L regimen approved for metastatic PDAC.•Recent trials of ≥2L conventional chemotherapies were generally encouraging, but most were single-arm phase 1 or 2 studies.•Recent trials of tyrosine kinase inhibitors have generally been negative.•Strategies to boost checkpoint inhibitor sensitivity have generally been disappointing. The aim of this review was to characterize the second- and later-line (≥2L) treatment landscape for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). This systematic literature review (PROSPERO: CRD42021279753) involved searches of MEDLINE® and Embase to identify results from prospective studies of ≥2L treatment options for metastatic pancreatic cancer published from 2016 to 2021. Publications were screened according to predetermined eligibility criteria; population-level data were extracted using standardized data fields. Publication quality was assessed according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The data were analyzed descriptively, grouped by drug class. Sixty publications were identified, including 23 relating to comparative trials. GRADE assessment found that, of these 23 trials, 83% reported high or moderate-quality evidence. Of the publications relating to comparative trials, nine (three trials) reported favorable results: the pivotal phase 3 NAPOLI-1 trial for liposomal irinotecan; a phase 3 trial of non-liposomal irinotecan within the FOLFIRINOX regimen; and a phase 2 trial of eryaspase plus chemotherapy. The level of unmet need for ≥2L treatment options for mPDAC remains high. Irinotecan-based regimens currently offer the greatest promise. Investigations into paradigm-changing agents and combination approaches continue.