Nanoliposomal irinotecan with 5-fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy: A real-world experience

Abstract

Background: Nanoliposomal irinotecan (nal-IRI), accompanied by 5-fluorouracil (5-FU) and leucovorin (LV), is an effective and safe therapy for patients in whom metastatic pancreatic ductal adenocarcinoma has progressed after gemcitabine-based chemotherapy. Our aim was to evaluate the effectiveness and safety of a nal-IRI + 5-FU/LV regimen for patients with metastatic pancreatic cancer and gemcitabine-based treatment failure in the real world. Methods: We retrospectively collected the baseline characteristics, treatment courses and dosage, treatment response, overall survival (OS), progression-free survival (PFS), and adverse effects of patients treated with the nal-IRI-based regimen at Taipei Veterans General Hospital. Results: Sixty-seven patients who received the nal-IRI + 5-FU/LV regimen from August 2018 to June 2019 were identified. Their median age was 65 years and 52% were male. Most patients had an Eastern Cooperative Oncology Group performance status of 0 to 1, but patients with an Eastern Cooperative Oncology Group performance status of 2 to 4 before initiation of the nal-IRI regimen were also enrolled (31%). The median dose intensity was 40.4 mg/m 2 and the median treatment duration was 8.3 weeks (range: 5 days-75.7 weeks). Objective response and disease control rates were 10.4% and 38.8%, respectively. The median OS) was 7.9 months (95% confidence interval [CI]: 5.6-10.1 months) and the median PFS was 2.9 months (95% CI: 1.6-4.1 months). Elevated total bilirubin (hazard ratio [HR]: 4.31, 95% CI: 1.21-15.30, p = 0.024), carcinomatosis (HR: 3.75, 95% CI: 1.46-9.66, p = 0.006), and previous treatment with irinotecan (HR: 4.86, 95% CI: 1.67-14.10, p = 0.004) were associated with a worse OS. Previous treatment with irinotecan (HR: 3.03, 95% CI: 1.22-7.49, p = 0.02) was associated with a worse PFS. The most common all-grade adverse effects were anemia (73.9%), nausea (66.2%), and fatigue (61.5%). The most common grade 3-4 adverse effects were neutropenia (21.5%), anemia (18.5%), and diarrhea (15.4%). Conclusion: Clinically, nal-IRI + 5-FU/LV is effective and tolerable at reduced doses in patients with metastatic pancreatic adenocarcinoma that has progressed after gemcitabine-based therapy

Treatment Effect and Safety of Nanoliposomal Irinotecan with Fluorouracil and Folinic Acid after Gemcitabine-Based Therapy in Patients with Advanced Pancreatic Cancer: A Multicenter, Prospective Observational Study

“…Second, in a previous study on the efficacy of nal-IRI/FF [ 11 ], patients who experienced no cancer progression with irinotecan treatment showed improved survival compared to those with prior cancer progression with irinotecan (mOS: 7.7 vs. 3.9 months). Smith et al [ 13 ] and Yu et al [ 14 ] showed a similar result in patients with APC who had been treated with irinotecan. Thus, we excluded patients who had received prior irinotecan-containing therapy to assess the effect of nal-IRI/FF without being confounded by the history of irinotecan administration.…”

Organ- or function-preservation surgery is recommended, but who is a candidate?

“…13 Pancreatic cancer is a well-known disease with the worst prognosis compared to other cancers. 14 We don’t know whether the cancer risk that occurred in nearly one-fifth of ADP patients is acceptable by the authors’ concept, but we are very concerned with this risk. Recently, prophylactic surgery for certain types of cancer, such as breast and ovarian cancers, has been re-considered.…”

Risk Factors for Adverse Events of Nanoliposomal Irinotecan Plus 5-Fluorouracil and L-leucovorin

“…There are many reports on predictors of treatment-response by nal-IRI-based therapy. In particular, CAR, NLR, GPS, total bilirubin, carcinomatosis, and previous treatment with irinotecan have been significantly associated with overall survival (3)(4)(5)(6)(7)(8). However, no study has reported the risk factors for the adverse events during nal-IRI/FL treatment based on the analysis of factors other than the UGT1A1 polymorphism in clinical settings.…”

“…Based on this trial result, the regulatory agency in Japan has approved the nal-IRI plus 5-FU and L-leucovorin (nal-IRI/FL) combination therapy. Particularly interesting studies focused on predictors of treatment-response by nal-IRI-based therapy in patients with pancreatic cancer have indicated that C-reactive protein/albumin ratio (CAR), neutrophil/lymphocyte ratio (NLR), Glasgow prognostic score (GPS), total bilirubin, carcinomatosis, and previous irinotecan treatment are significantly associated with overall survival (3)(4)(5)(6)(7)(8).…”