Oncology
Metastatic Pancreatic Cancer
Impact of Modern Regimens on the Treatment Landscape in Metastatic Pancreatic Cancer
Overview
Clinical Study Title:
Liposomal irinotecan in gemcitabine-refractory metastatic pancreatic cancer: efficacy, safety and place in therapy
Clinical Study Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. The majority of patients are diagnosed with locally advanced or metastatic disease with a prognosis of short months. Therapeutic options are limited and, until recently, there was no standard second-line chemotherapy option. Liposomal constructs have been engineered to encapsulate chemotherapy, thereby preventing premature metabolism, improving distribution, and minimizing toxicity. Favorable preclinical data on liposomal irinotecan and early-phase trials, led to a recently published phase 3 trial of liposomal irinotecan in combination with fluorouracil and folinic acid in patients with metastatic PDAC, who progressed after gemcitabine-based chemotherapy. As a direct result, the US Food and Drug Administration (FDA) and European Medicines Agency have approved the use of liposomal irinotecan in this setting. However, first-line treatment options for this disease now include the combination regimen, FOLFIRINOX, in patients with good performance status, and the role of second-line combination treatment with liposomal irinotecan in this setting is unclear. Recent advances have changed the therapeutic landscape, as clinicians are now able to choose a sequential approach to treatment tailored to the individual patient characteristics. This article reviews current treatment options for metastatic PDAC and focuses on the efficacy, safety, and place in therapy of liposomal irinotecan.
Reference:
Kipps E, Young K, Starling N. Liposomal irinotecan in gemcitabine-refractory metastatic pancreatic cancer: efficacy, safety and place in therapy. Ther Adv Med Oncol. 2017;9(3):159-170.
Expert Commentary
Thomas A. Abrams, MD
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Treatment options for patients with metastatic pancreatic cancer (MPC) have greatly improved in recent years, including the use of recently approved regimens such as liposomal irinotecan + 5-FU/LV. This article nicely demonstrates how modern regimens, such as FOLFIRINOX and liposomal irinotecan + 5-FU/LV, have affected the treatment landscape. Kipps et al reviewed both preclinical and clinical data on liposomal irinotecan, which was recently FDA approved with 5-FU/LV for treatment of MPC after progression on gemcitabine-based chemotherapy. The authors concluded that although the combination of liposomal irinotecan and 5-FU/LV demonstrated a significant overall survival advantage in the randomized, phase 3 NAPOLI-1 trial (6.1 vs 4.2 months in the 5-FU/LV arm [P=0.012]), the experimental arm toxicity rates (27% grade 3/4 neutropenia; 50% any-grade diarrhea, nausea, and vomiting) demonstrate the critical importance of patient selection. However, for patients in whom first-line FOLFIRINOX is not the preferred option, gemcitabine-based chemotherapy followed by liposomal irinotecan and 5-FU/LV is a reasonable treatment strategy for a subset of patients. |
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“This article nicely demonstrates how these modern regimens, such as liposomal irinotecan + 5-FU/LV and FOLFIRINOX, have impacted the treatment landscape.”
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