Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group

Abstract

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) was effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma (mPAC) that progressed on gemcitabine-based therapy in the global NAPOLI-1 trial. Real-world data may further clarify the outcomes and safety profile of nal-IRI + 5-FU/LV in clinical practice. Methods: This retrospective analysis included patients with mPAC who received nal-IRI + 5-FU/LV following gemcitabine-based therapy under a Managed Access Program in Korea. Results: From January 2017 to April 2018, 86 patients across 10 institutions received nal-IRI + 5-FU/LV (median age, 61 years; 60% male; ECOG performance status, 0–1). A total of 35 (41%) and 51 (59%) patients had received less than two and two or more lines of chemotherapy before inclusion, respectively. At a median follow up of 6.4 months, median overall survival (OS) was 9.4 months (95% confidence interval [CI] 7.4–11.4) and median progression-free survival (PFS) was 3.5 months (95% CI 1.3–5.7). Six-month OS and PFS rates were 65.1% and 37.5%, respectively. Objective response and disease control rates were 10% and 55%, respectively. Most common grade 3–4 toxicities were neutropenia (37.2%), nausea (10.5%), vomiting (9.3%), anorexia (8.1%) and diarrhoea (4.7%). Conclusion: Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy.

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 ).…”

“…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 ].…”

“…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 ]. Where stated, nal-IRI + 5-FU/LV was administered as a second-line or earlier therapy in 41–73% of patients [ 24 – 27 , 30 – 32 ] and as a third-line or later therapy in 25–59% of patients [ 24 – 27 , 30 – 32 ]. Of note, 44% and 76% of patients in multicentre studies from South Korea [ 27 ] and Italy [ 30 ], respectively, previously received nab-paclitaxel + gemcitabine as first-line therapy.…”

“…Where stated, nal-IRI + 5-FU/LV was administered as a second-line or earlier therapy in 41–73% of patients [ 24 – 27 , 30 – 32 ] and as a third-line or later therapy in 25–59% of patients [ 24 – 27 , 30 – 32 ]. Of note, 44% and 76% of patients in multicentre studies from South Korea [ 27 ] and Italy [ 30 ], respectively, previously received nab-paclitaxel + gemcitabine as first-line therapy. Moreover, 45% and 49% of patients in single-centre studies from the USA [ 25 ] and Austria [ 24 ], respectively, who were administered nal-IRI + 5-FU/LV as a second-line therapy had previously received nab-paclitaxel + gemcitabine (or nab-paclitaxel + gemcitabine or gemcitabine alone [ 25 ]) as first-line therapy (Table 3 ).…”

“… Paluri et al [ 28 ] [USA] 51 [NR] NR OS 5.1 a 11 (nal-IRI + 5-FU/LV as 2nd line ther) j 4.7 (no prior IRI) 3.9 (prior IRI) PFS 2.3 a 9 (nal-IRI + 5-FU/LV as 2nd line ther.) j 3.2 (no prior IRI) 2.2 (prior IRI) Pellino et al [ 30 ] [Italy] 296 [69 (range 30–82)] 1: 72 ≥ 2: 25 OS 7.1 a PFS 3.3 a Su et al [ 26 ] [Taiwan] 44 [60 (range 26–80)] 1: 73 ≥ 2: 27 OS 6.6 a PFS 2.5 a Yoo et al [ 27 ] [South Korea] 86 [61 (range 37–79)] 0–1: 40.7 2: 41.9 ≥ 3: 17.5 OS 9.4 a Not reached (< 2 prior lines of ther.) 7.9 (≥ 2 prior lines of ther.)…”