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J Gastrointest Oncol. 2017 Dec;8(6):925-935. doi: 10.21037/jgo.2017.09.05.

A phase 2 trial of personalized cytotoxic therapy based on tumor immunohistochemistry in previously treated metastatic pancreatic cancer patients.

Author information

Honor Health Research Institute, Scottsdale, AZ, USA.
Mayo Clinic Cancer Center, Phoenix, AZ, USA.
Translational Genomics Research Institute, Phoenix, AZ, USA.
Department of Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Human Therapeutics Division, Intrexon Corporation, Germantown, MD, USA.
Cancer Research And Biostatistics(CRAB), Seattle, WA, USA.
Sheikh Ahmed Pancreatic Cancer Research Center, UT MD Anderson Cancer Center, Houston, TX, USA.
Caris Life Sciences, Phoenix, AZ, USA.
Beth Israel Deaconess Medical Center, Boston, MA, USA.
Centro Nacional de Investigaciones Oncológicas and Hospital de Madrid, Madrid, Spain.



The choice of a regimen in metastatic pancreatic cancer patients following progression on 1st line therapy is empiric and outcomes are unsatisfactory. This phase II study was performed to evaluate the efficacy of therapy selected by immunohistochemistry (IHC) in these patients following progression after one or more therapies.


Eligible patients underwent a percutaneous biopsy of a metastatic lesion and treatment selection was determined by IHC. The study required 35 evaluable patients (power of 86%) for detecting a true 1-year survival rate of >20%.


A tumor biopsy was performed in 48 of 49 accrued patients. Study therapy was not given (n=13) either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5). The demographics of evaluable patients (n=35) are male/female (59%/41%), with age range 34-78 years (median 63 years). Patients had 1-6 prior regimens (median of 2). The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, excision repair cross-complementation group 1 protein (ERCC1), and osteonectin secreted protein acidic and rich in cysteine (SPARC). Commercially available treatment regimens prescribed included FOLFIRI, FOLFOX, irinotecan, and doxorubicin. The response (RECIST) was 9%, the median survival was 5.6 months (94% CI, 3.8-8.2), and the 1-year survival was 20% (95% CI, 7-33%).


In all patients, IHC assays resulted in identification of at least two targets for therapy and a non-cross resistant regimen could be prescribed for therapy with evidence of some benefit. An IHC based treatment strategy is feasible and needs validation in larger studies.


Array comparative genomic hybridization (aCGH); immunohistochemistry (IHC); molecular profiling (MP); pancreatic cancer; phase II clinical trial

Conflict of interest statement

Conflicts of Interest: This work was presented in part at the American Association for Cancer Research; 103rd Annual Meeting (LB-221 and A 3697), 2012, Chicago, IL, USA. RK Ramanathan: meeting honorarium and travel expenses from Caris Life Sciences; DD Von Hoff: consultant and stock options, Caris Life Sciences; Z Gatalica, J Xiu: employment and stock options, Caris Life Sciences. The other authors have no conflicts of interest to declare.

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