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Beyond first-line chemotherapy for advanced pancreatic cancer: an expanding array of therapeutic options?

ABSTRACT: While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8 mo, highlighting the very poor prognosis of patients who are candidates for such treatment. Targeted therapies studied in this chemotherapy-refractory setting, meanwhile, have produced even worse efficacy results. In the current article, we review the clinical evidence for treatment of refractory disease, primarily in patients who have progressed on front-line gemcitabine-based chemotherapy. In the process, we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting, including how to select an appropriate control arm given the absence of a well-established reference standard, and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.

SUBMITTER: Walker EJ

PROVIDER: S-EPMC3942828 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Beyond first-line chemotherapy for advanced pancreatic cancer: an expanding array of therapeutic options?

Walker Evan J EJ Ko Andrew H AH

World journal of gastroenterology 20140301 9

While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range o ...[more]

PMID: 24605022

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Project description:Urothelial carcinoma (UC) is a frequently diagnosed tumor and an important cause of cancer deaths worldwide. Until a few years ago, despite the unquestioned role of platinum-based chemotherapy, therapeutic choices beyond the first line were limited and related to unsatisfactory outcomes. Metastatic UC has always been associated with a poor prognosis, with overall survival only slightly above a year. In the recent past, huge progress has been made in our understanding of the molecular and genomic disease characteristics, to enable stratification of patients in terms of prognosis and treatment responses. Unfortunately, we still do not have the perfect combination of clinical biomarkers to tailor the optimal treatment for each patient, despite making several efforts in this direction. The therapeutic arsenal has been augmented by immune checkpoint inhibitors (ICIs), which nowadays represent the backbone of the second-line setting. Equally revolutionary was the FDA's approval of erdafitinib, a potent fibroblast growth factor receptor (FGFR) inhibitor, the use of which is reserved for patients whose tumor harbors specific FGF pathway alterations. Recently, the therapeutic landscape of metastatic UC has been enhanced by the introduction of novel compounds, consisting of antibody-drug conjugates (ADCs). Enfortumab vedotin is an antibody targeting nectin-4, a cell adhesion molecule highly expressed in UC, conjugated to monomethyl auristatin E (MMAE), a microtubule-disrupting agent. Sacituzumab govitecan is a humanized monoclonal antibody targeting Trop-2, a transmembrane glycoprotein, conjugated to the active metabolite of irinotecan. These two compounds have received accelerated approval by the FDA in patients pretreated with platinum-based chemotherapy and immunotherapy. Several ongoing trials are investigating the role of ICIs combined with chemotherapy, antiangiogenic drugs, or other ICIs, as well as the efficacy of PARP inhibitors and target therapies, hoping to provide information for some important unmet needs. In this review, we aim to evaluate the current potential treatment options after first-line chemotherapy.

Dataset Information

Beyond first-line chemotherapy for advanced pancreatic cancer: an expanding array of therapeutic options?

Publications

Beyond first-line chemotherapy for advanced pancreatic cancer: an expanding array of therapeutic options?

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