Research on Liposomal Irinotecan in Combination with 5-FU/LV for Metastatic Pancreatic Ductal Adenocarcinoma

Objective To systematically review the published clinical and economic research on liposomal irinotecan in combination with 5-FU/LV for metastatic pancreatic ductal adenocarcinoma(mPDAC)at home and abroad.Methods PubMed,Cochrane Library,Embase,CBM,CNKI,Wan Fang data,CRD database and health technology assessment official websites were searched to collect clinical and economic studies on liposomal irinotecan for mPDAC.Results and Conclusion Nine clinical studies and four economic studies were included.The result of clinical studies showed that liposomal irinotecan in combination with 5-FU/LV could extend survival with good drug compliance in patients with mPDAC who progressed on prior gemcitabine-based therapy.This agent represented a new treatment option for second-line chemotherapy in these patients.The results of the economic evaluations failed to reach a consistent conclusion due to different economic levels in various countries.

How to improve metastatic pancreatic ductal adenocarcinoma patients’selection:Between clinical trials and the real-world

As underlined in the minireview by Blomstrand et al,given the poor prognosis and the paucity of data on a therapeutic sequence in pancreatic ductal adenocarcinoma(PDAC),additional randomized controlled trials and real-world evidence studies addressing current and novel regimens are needed.The real-world outcomes of first-line chemotherapy regimens such as FOLFIRINOX and gemcitabine/nab-paclitaxel are thoroughly reviewed and seem to be largely generalizable in a real-world context.Regarding second-line chemotherapy,the key question about the optimal sequence of regimens remains uncertain.Precisely in this setting,it is therefore useful to encourage the implementation of clinical studies that may contribute to the scarcity of data available up to now.We report our experience with a small group of patients treated with second-line liposomal irinotecan(nal-IRI)plus 5-fluorouracil and leucovorin.To improve the treatment of patients affected by PDAC,it is useful to identify subgroups of patients who may benefit from target treatments(e.g.,BRCA mutant)and it is also important to focus on any prognostic factors that may affect the survival and treatment of these patients.

Survival outcomes of conversion surgery for metastatic pancreatic ductal adenocarcinoma after neoadjuvant therapy

Objective:To evaluate the survival outcomes of patients who underwent conversion surgery for metastatic pancreatic ductal adenocarcinoma(mPDAC)after neoadjuvant therapy(NAT)and to identify potential candidates that may benefit from this treat-ment strategy.Background:The role and eligibility population of conversion surgery for mPDAC remains controversial in the era of NAT.Methods:A consecutive cohort of patients diagnosed with mPDAC and treated with NAT followed by conversion surgery be-tween 2019 and 2021 were confirmed from a prospective database maintained by the Department of Pancreatic Hepatobiliary Surgery of Changhai Hospital.In accordance with residual metastases and technical resectability after NAT,patients were classi-fied as the complete pathological response of metastases(ypM0)resection group,residual metastases(ypM1)resection group,and exploration group.Median overall survival(mOS)was calculated using the Kaplan-Meier method,uni-and multivariable cox regression was performed to identify clinicopathological predictors of OS.Results:A total of 244 patients with mPDAC were identified from the prospective database,with 19(7.8%)patients who un-derwent ypM0 resection,22(9.0%)underwent ypM1 resection,and 23(9.4%)underwent explorative laparotomy.The mOS was 32.6 months for ypM0 resected patients,15.1 months for ypM1 resected patients,and 13.4 months for those who underwent explorative laparotomy(P<.001).Univariable and multivariable Cox regression analyses confirmed that ypM0 resection,normal-ization of preoperative CA19-9 levels,and continued adjuvant therapy were independent prognostic factors of conversion surgery for mPDAC after NAT.Subgroup analyses revealed that oligometastases and continued adjuvant therapy were associated with improved prognosis in the ypM1 resection group.Conclusion:In patients with mPDAC who underwent NAT followed by conversion surgery,the complete pathological response of metastases,normalization of preoperative CA19-9 levels,and continued adjuvant therapy were independent risk factors for prognosis.Patients with residual oligometastases after treatment were expected to prolong survival through resection.These patients may benefit from conversion surgery and should be potential candidates for this treatment strategy.