Pancreatic Adenocarcinoma: Management of Advanced Unresectable and Metastatic Disease

Conclusion

Pancreatic adenocarcinoma is the most lethal of all the gastrointestinal malignancies. FOLFIRINOX and gemcitabine/nab-paclitaxel are superior to gemcitabine monotherapy for patients with advanced unresectable and/or metastatic pancreatic cancer who are candidates for more aggressive therapy and are considered first-line therapies. Early data on the gemcitabine, nab-paclitaxel, and cisplatin combination appears to show superior efficacy. Second-line therapies are selected based on the patient’s performance status, first-line regimen, and residual toxicities from the prior regimen; options include gemcitabine/nab-paclitaxel, FOLFIRINOX (± oxaliplatin or irinotecan), single-agent gemcitabine (elderly frail patients), fluorouracil and liposomal-irinotecan, or referral for a clinical trial. The main challenge with pancreatic cancer is the development of stroma around the tumor, which abrogates drug delivery, allows for tumor growth in a hypoxic microenvironment, alters the metabolomics, and causes an immunosuppressive microenvironment. Drugs that target the microenvironments, such as hedgehog pathway inhibitors, have failed to show any clinical benefit, and we hope to see more efficacious microenvironment-targeted novel drugs in the future. In addition, immunotherapy has not shown any significant efficacy in clinical trials and many trials are still ongoing.