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. 2018 Apr 10;9(27):19396-19405.
doi: 10.18632/oncotarget.25036.

Advanced pancreatic cancer: a meta-analysis of clinical trials over thirty years

Bradley R Hall  1   2 , Andrew Cannon  2 , Pranita Atri  2 , Christopher S Wichman  3 , Lynette M Smith  3 , Apar K Ganti  4   5 , Chandrakanth Are  1 , Aaron R Sasson  6 , Sushil Kumar  2 , Surinder K Batra  2   7
Affiliations

Advanced pancreatic cancer: a meta-analysis of clinical trials over thirty years

Bradley R Hall et al. Oncotarget. .

Abstract

Background: In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC.

Materials and methods: All Phase 2-4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis. Publications obtained through PubMed and www.ClinicalTrials.gov were cross-referenced to identify additional trials. Trials enrolling fewer than 50% of study participants with metastatic disease were excluded.

Results: Of 19,488 patients enrolled in 151 clinical trials, 84% had metastatic disease and 16% had locally advanced pancreatic cancer. In clinical trials published from 1986 to 2016, the weighted median overall survival (wMOS) increased by 3.0 months. The median wMOS was higher in combination therapy (7.31 months, IQR 5.4 to 8.5) compared to non-gemcitabine, single-agent therapy (4.76 months, IQR 3.5 to 6.0), gemcitabine monotherapy (6.48 months, IQR 5.9 to 7.2), and gemcitabine plus single-agent therapy (7.09 months, IQR 6.3 to 8.2). Of all regimens used in more than one study arm, FOLFIRINOX had the highest wMOS (10.9 months).

Conclusions: Regardless of treatment regimen, survival rates in PDAC have minimally improved over time. Of drugs used in two or more study arms, only FOLFIRINOX has a wMOS greater than ten months. Emphasis should, therefore, be placed on identification of novel targets that promote early diagnosis and intervention.

Funding: The authors on this manuscript are in parts, supported by grants from the National Institutes of Health (EDRN U01 CA200466, SPORE P50 CA127297, R01 CA183459, R21 AA026428 and R01 CA 195586).

Keywords: chemotherapy; meta-analysis; metastasis; pancreatic ductal adenocarcinoma; survival.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors have no financial interests to disclose.

Figures

Figure 1
Figure 1. Flow diagram showing methods for inclusion and exclusion of studies in meta-analysis
For the PubMed search, the ‘phase’ search term was limited to the title/abstract, whereas ‘pancreatic cancer’ was not restricted by search location. For the www.clinicaltrials.gov search, results were limited to completed interventional trials with results. Primary exclusion criteria included: 1) trials in which any patient had ampullary carcinoma, intraductal papillary mucinous neoplasm, hepatobiliary carcinoma, or any diagnosis other than PDAC; 2) publications not available in English; 3) trials which included any patient with resectable or borderline resectable disease; 4) trials evaluating either adjuvant or primarily radiation therapy; 5) sub-analyses of previously published clinical trials; and 6) meeting proceedings and abstracts without an associated published manuscript.
Figure 2
Figure 2. Forest plot of treatment efficacy
Weighted MOS and interquartile range (IQR) for all treatment regimens are plotted.
Figure 3
Figure 3. Trends in weighted MOS
Drug regimens are listed in order of publication in large phase three clinical trials [1, 11, 28, 29].
See this image and copyright information in PMC

References

    1. Burris HA, 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13. - PubMed
    1. National Cancer Institute. DCCPS. Surveillance Research Program Surveillance, Epidemiology, and End Results (SEER) Research Data (1973–2014) Available: www.seer.cancer.gov [accessed June 15, 2017]
    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30. - PubMed
    1. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21. - PubMed
    1. Vogelzang NJ, Benowitz SI, Adams S, Aghajanian C, Chang SM, Dreyer ZE, Janne PA, Ko AH, Masters GA, Odenike O, Patel JD. Clinical cancer advances 2011: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2011;30:88–109. - PubMed