4.4 Review

Harnessing the Immune System in Pancreatic Cancer

Journal

CURRENT TREATMENT OPTIONS IN ONCOLOGY
Volume 19, Issue 10, Pages -

Publisher

SPRINGER
DOI: 10.1007/s11864-018-0566-5

Keywords

Metastatic pancreatic cancer; Immunotherapy; Microsatellite instability; Tumor microenvironment

Categories

Funding

  1. Celgene
  2. EMD Serono
  3. Hoffman-La Roche
  4. Incyte
  5. Oncolytics Biotech
  6. Synta Pharmaceuticals
  7. Bristol-Myers Squibb
  8. Advaxis
  9. Lilly
  10. Novartis
  11. AbbVie
  12. Immunomedics
  13. Taiho
  14. Genentech/Roche
  15. Bayer
  16. Pharmacyclics
  17. Five Prime
  18. Loxo
  19. NATIONAL CANCER INSTITUTE [K12CA090625] Funding Source: NIH RePORTER

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Managing patients with metastatic pancreatic adenocarcinoma (mPDA) is a challenging proposition for any treating oncologist. Although the potency of first-line therapies has improved with the approvals of FOLFIRINOX and gemcitabine plus nab-paclitaxel, many patients are unable to derive significant benefit from later lines of therapy upon progression. Enrollment on clinical trials remains among the best options for patients with mPDA in all lines of therapy. At our institution, we routinely check for microsatellite instability (MSI-H) and perform next-generation sequencing (NGS) at the time of diagnosis in all good performance status mPDA patients. Although MSI-H status is only found in 1% of patients with mPDA, given pembrolizumab's tissue-agnostic approval for MSI-H tumors in later-line settings, it is a viable option when deciding on subsequent lines of therapy. Any use of immune therapy in mPDA is investigational outside the MSI-H setting. NGS can identify BRCA or other DNA damage response (DDR) defects in patients which can predict sensitivity to platinum-based therapies and influence choice of both initial and later lines of therapy. It can also identify rare actionable genomic alterations such as HER2 (2%) and TRK fusions (0.1%) and offer patients the option of enrollment on clinical trials with agents targeting these or other identified alterations. We believe enrolling mPDA patients on clinical trials with immune-modulating agents is critical to determine if there are other patient subsets, outside of the MSI-H setting, who would benefit from these approaches. Immunotherapy's general tolerability and potential to generate durable responses make it particularly appealing for mPDA patients. Although single-modality immunotherapy such as checkpoint inhibitors or vaccines have not demonstrated efficacy in this disease, combinatorial strategies targeting unique aspects of PDA including the tumor microenvironment and desmoplastic stroma have shown preclinical or early-phase success. Validating these treatments with later-phase prospective studies is essential to making immunotherapy a routine component of the treatment armamentarium for mPDA patients.

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