A network meta-analysis (NMA) of randomized controlled trials (RCT) of chemotherapy regimens for metastatic pancreatic cancer (mPC).

Authors

null

Gillian Gresham

University of Ottawa, Ottawa, ON, Canada

Gillian Gresham , Sharlene Gill , George A Wells , Derek J. Jonker

Organizations

University of Ottawa, Ottawa, ON, Canada, British Columbia Cancer Agency, Vancouver, BC, Canada, The Ottawa Hospital Cancer Center, Ottawa, ON, Canada

Research Funding

No funding sources reported

Background: Recent RCTs suggest a survival benefit for combination therapy in mPC compared to gemcitabine alone. Such combinations include FOLFIRINOX and gemcitabine plus nab-paclitaxel (G+nab-P). Survival and safety outcomes of these regimens were analyzed using gemcitabine as the reference comparator. Methods: Systematic review and NMA included data from reported phase III RCTs meeting quality standards and compared chemotherapy treatment to gemcitabine for mPC between 2000 and 2013. Excluded were trials assessing locally advanced pancreatic cancer. Following inter-trial heterogeneity assessment (patient characteristics, trial methodologies, treatment protocols), Bayesian NMAs were conducted for primary (overall survival [OS]) and secondary (progression free survival [PFS]) outcomes, overall response rate [ORR], and safety. Results: 27 studies were included involving 10 429 patients and 18 different treatments. No significant heterogeneity was observed between trials. When indirectly compared, FOLFIRINOX, PEFG and G+nab-P were top ranked for OS, PFS and ORR (Table). Comparing FOLFIRINOX and G +nab-P, there was no significant difference in odds ratios (OR) for febrile neutropenia, diarrhea or sensory neuropathy. FOLFIRINOX caused more gr3-4 neutropenia (OR 1.85 (95%Cl 1.1-3.4),p<0.05), and G+nab-P trended more gr3-4 fatigue (OR 2.03 95% Cl 0.95-3.8). Conclusions: Survival and safety outcomes were comparable amongst the three regimens identified from this network meta-analysis for mPC. FOLFIRINOX tended towards a greater survival benefit over G+nab-P and PEFG although comparisons did not reach statistical significance.Head-to-head trials between FOLFIRINOX, G+nab-P and PEFG are needed to further compare the survival benefits and safety profiles of these treatments.

Direct comparison OS PFS
FOLFIRINOX vs. Gem 0.57 (0.45-0.73) 0.47 (0.37-0.59)
G+nab-P vs. Gem 0.72 (0.62-0.835) 0.69 (0.581-0.821)
PEFG* vs. Gem 0.65 (0.43-0.99) 0.51 (0.42-0.96)
Indirect comparison
FOLFIRINOX vs. G+nabP 0.81 (0.55-1.14) 0.70 (0.44-1.04)
FOLFIRINOX vs. PEFG* 0.90 (0.55-1.47) 0.95 (0.52-1.62)

* PEFG – cisplatin, epirubicin, 5FU, gemcitabine.

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Abstract Details

Meeting

2013 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal (Noncolorectal) Cancer

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Pancreatic Cancer

Citation

J Clin Oncol 31, 2013 (suppl; abstr 4050)

DOI

10.1200/jco.2013.31.15_suppl.4050

Abstract #

4050

Poster Bd #

17D

Abstract Disclosures