A real-world analysis of second-line treatment options in pancreatic cancer: liposomal-irinotecan plus 5-fluorouracil and folinic acid

Abstract

Background: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) is a novel treatment option for gemcitabine-pretreated metastatic pancreatic adenocarcinoma (PAC) patients, but real-world evidence is rare. Our aim was to determine the effectiveness and tolerability of this regimen in advanced PAC patients and to compare it with oxaliplatin plus fluoropyrimidines in the second-line setting after failure of gemcitabine. Methods: This is a retrospective single-center analysis of all patients who have been treated with nal-IRI plus 5-FU/LV. To compare its effectiveness with other second-line treatment options, all patients who had received oxaliplatin plus fluoropyrimidines after gemcitabine-based chemotherapy were also eligible for analysis. Results: Fifty-two patients were treated with nal-IRI plus 5-FU/LV between April 2016 and August 2018. The median progression-free survival (PFS) was 3.84 months and the median overall survival (OS) was 6.79 months. Median OS from the beginning of the treatment for advanced disease was 19.9 months. Median PFS in patients that received nal-IRI plus 5-FU/LV as second-line treatment after gemcitabine-based chemotherapy was 4.49 months whereas median PFS in a matched cohort of patients treated with oxaliplatin plus fluoropyrimidines was 3.44 months ( p = 0.007). Between these two groups the median OS of patients with CA 19-9 levels above the statistical median (⩾772.8 kU/l) differed significantly (9.33 versus 6.18 months, p = 0.038). Conclusion: Our data confirms the effectiveness of nal-IRI plus 5-FU/LV treatment as a well-tolerated regimen in the treatment of advanced PAC and extends available data on its use as a second-line treatment option when compared with oxaliplatin plus fluoropyrimidines.

Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma

“…2.1 ). More recently, the effectiveness of this combination has been evaluated in several retrospective, observational (real-world evidence) studies from one [ 24 – 26 ] or more [ 27 – 32 ] institutions in Austria [ 24 ], Italy [ 30 ], South Korea [ 27 ], Taiwan [ 26 ] or the USA [ 25 , 28 , 29 , 31 , 32 ] (Sect. 2.2 ).…”

“…Real-world studies investigating nal-IRI + 5-FU/LV have enrolled individuals ( n = 44–296) with advanced PDAC (i.e. unresectable, locally advanced or metastatic disease) that had progressed following gemcitabine-based chemotherapy in the neoadjuvant or adjuvant setting, or in a prior line of treatment for advanced disease [ 24 – 32 ] (some results only available as an abstract and/or poster [ 28 , 30 , 32 ]). The median age of study populations was 60–69 years, 38–61% were males and, where specified, 54–100% of evaluable patients had ECOG PS 0–1, and 61–83% of evaluable patients had elevated CA 19-9 levels [ 24 – 27 , 30 – 32 ].…”

“…unresectable, locally advanced or metastatic disease) that had progressed following gemcitabine-based chemotherapy in the neoadjuvant or adjuvant setting, or in a prior line of treatment for advanced disease [ 24 – 32 ] (some results only available as an abstract and/or poster [ 28 , 30 , 32 ]). The median age of study populations was 60–69 years, 38–61% were males and, where specified, 54–100% of evaluable patients had ECOG PS 0–1, and 61–83% of evaluable patients had elevated CA 19-9 levels [ 24 – 27 , 30 – 32 ]. Liver, lung and peritoneal metastases were present in 57–73%, 9–31% and 25–36% of patients, respectively (Table 3 ); 23–58% had ≥ 2 metastatic sites [ 24 – 26 , 30 ].…”

Exploiting the relevance of CA 19-9 in pancreatic cancer

“…Applicability of CA 19-9 levels to determine therapeutic and prognostic responses in PDAC There have been numerous studies investigating the clinical relevance of CA 19-9 in pancreatic cancer, and to define its applicability in predicting either the responses or resistance to various treatments [28][29][30] . A summary of these investigations is given in Table 2.…”

“…A summary of these investigations is given in Table 2. Kieler et al [28] evaluated CA 19-9 levels in response to chemotherapy with nanoliposome irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) as a second-line treatment for PDAC and compared it with oxaliplatin plus fluoropyrimidines. The findings revealed that at the start of therapy, the median progression-free survival (PFS) was significantly longer in patients who received nal-IRI plus 5 FU/LV compared to the median PFS in patients treated with oxaliplatin plus fluoropyrimidines.…”