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Evolving treatment landscape for early and advanced pancreatic cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma is an infrequent cancer with a high disease related mortality rate, even in the context of early stage disease. Until recently, the rate of death from pancreatic cancer has remained largely similar whereby gemcitabine monotherapy was the mainstay of systemic treatment for most stages of disease. With the discovery of active multi-agent chemotherapy regimens, namely FOLFIRINOX and gemcitabine plus nab-paclitaxel, the treatment landscape of pancreatic cancer is slowly evolving. FOLFIRINOX and gemcitabine plus nab-paclitaxel are now considered standard first line treatment options in metastatic pancreatic cancer. Studies are ongoing to investigate the utility of these same regimens in the adjuvant setting. The potential of these treatments to downstage disease is also being actively examined in the locally advanced context since neoadjuvant approaches may improve resection rates and surgical outcomes. As more emerging data become available, the management of pancreatic cancer is anticipated to change significantly in the coming years.

SUBMITTER: Lau SC

PROVIDER: S-EPMC5534396 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:The approval of targeted therapies for metastatic colorectal cancer (mCRC) has led to important improvements in patient outcomes. However, it is still necessary to increase individualisation of treatments based on tumour genetic profiles to optimise efficacy, while minimising toxicity. As such, there is currently great focus on the discovery and validation of further biomarkers in mCRC, with many new potential prognostic and predictive markers being identified alongside developments in patient molecular profiling technologies. Here, we review data for validated and emerging biomarkers impacting treatment strategies in mCRC. We completed a structured literature search of the PubMed database to identify relevant publications, limiting for English-language publications published between 1 January 2014 and 11 July 2018. In addition, we performed a manual search of the key general oncology and CRC-focused congresses to identify abstracts reporting emerging mCRC biomarker data, and of ClinicalTrials.gov to identify ongoing clinical trials investigating emerging biomarkers in mCRC and/or molecular-guided clinical trials. There is solid evidence supporting the use of BRAF status as a prognostic biomarker and DYPD, UGT1A1, RAS, and microsatellite instability as predictive biomarkers in mCRC. There are a number of emerging biomarkers that may prove to be clinically relevant in the future to have prognostic (HPP1 methylation), predictive (HER3, microRNAs, anti-angiogenic markers, and CRC intrinsic subtypes), or both prognostic and predictive values (HER2, CpG island methylator phenotype, tumour mutational load, gene fusions, and consensus molecular subtypes). As such, new biomarker-led treatment strategies in addition to anti-epidermal growth factor receptor and anti-angiogenetic treatments are being explored. Biomarkers that are not recommended to be tested in clinical practice or are unlikely to be imminently clinically relevant for mCRC include thymidylate transferase, ERCC1, PIK3CA, and PTEN. We highlight the clinical utility of existing and emerging biomarkers in mCRC and provide recommended treatment strategies according to the biomarker status. An update on ongoing molecular-guided clinical trials is also provided.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is currently ranked fourth place of cancer related mortality. Only a minority of 10-20% of patients with PDAC have a primarily resectable disease, while 50-60% of the patients are diagnosed with irresectable disease. A certain group of patients is defined as "borderline resectable", which is mainly relied to contact of the tumor to major abdominal vessels. For preoperative evaluation of resectability CT and MRI is commonly used. Although CT-scanning, which is the standard preoperative imaging modality, has striking limitations concerning evaluation of lymph node status as well as vessel involvement and approximately 20% of the patients are staged incorrectly. A central part of modern therapy of locally advanced or not primarily resectable PDAC is neoadjuvant therapy. Especially neoadjuvant chemotherapy according to the FOLFIRINOX protocol resulted in high resection rates of initially not resectable patients. Furthermore, treatment with FOLFIRINOX was shown to be an independent predictor of improved prognosis and resection after neoadjuvant treatment with FOLFIRINOX was associated with improved survival. Neoadjuvant treatment was able to increases the rates of R0 resection, which depicts an independent prognostic factor and FOLFIRINOX outmatched other treatment regimes (e.g., gemcitabine-based radio-chemotherapy) concerning achievement of a R0 resection. While most evidence of neoadjuvant treatment of PDAC is conferred by retrospective analysis, there is growing data from randomized controlled trials, confirming the beneficial effects of neoadjuvant therapy on the prognosis of PDAC. Thus, patients with borderline resectable and locally advanced PDAC should be evaluated for neoadjuvant treatment. If there is no progression of the disease during neoadjuvant treatment exploration with the goal of R0 resection should be performed. If possible, patients should be included in well-designed randomized controlled trials at specialized pancreatic centers.

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Evolving treatment landscape for early and advanced pancreatic cancer.

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