Neo-adjuvant therapy for pancreatic cancer: hope for the future

ABSTRACT

Introduction: In 2018, pancreatic ductal adenocarcinoma (PDAC) was the 3rd highest cause cancer related death in the United States. Worldwide estimates in 2018 indicate 458,918 cases diagnosed with 432,242 deaths. Standard therapy for decades for localized PDAC has been to pursue surgical resection for localized disease. For the individuals who are diagnosed with localized PDAC and undergo surgical resection, historical survival has been reported to be around 24 months. While recent advancements in the use of multiagent systemic therapy has allowed for greater survival benefit, adjuvant therapy does have limitations. Recently, neo-adjuvant therapy for PDAC has become more accepted in practice.

Areas covered: In this review, we will discuss the current guidelines for treatment of localized PDAC, the pros and cons of neo-adjuvant versus adjuvant therapy for PDAC, the utilization of available biomarkers for the management of PDAC, and future possibilities for clinical trials.

Expert commentary: Neo-adjuvant therapy for localized PDAC has tremendous promise in leading to greater survival by treating for micro-metastatic disease along with selecting for patients for better outcomes. Further work based upon molecular insights will lead to better biomarkers for treatment assessment along with improvements in treatment.

KEYWORDS:

• Pancreatic ductal adenocarcinoma
• neo-adjuvant therapy
• clinical trials
• review

Article Highlights

• Pancreatic ductal adenocarcinoma (PDAC) carries a poor 5 year survival, even in localized disease

• The paradigm of treatment of localized PDAC management utilizing up-front surgical resection has shown around a 20% 5 year survival.

• Most individuals diagnosed with localized PDAC likely have micrometastatic disease, which cannot be addressed by surgical resection alone. Furthermore, recovery from surgery may prevent an individual from receiving planned systemic chemotherapy, even if found to have margin positive or nodal positive disease let alone evidence of metastatic disease on follow up imaging.

• The utilization of neoadjuvant therapy with multi-agent chemotherapy may allow for better survival of patients with PDAC in addition to selecting out those who may have an aggressive disease course that manifest metastatic disease early.

• Utilization of a multi-modality treatment strategy incorporating chemotherapy, radiation therapy, and surgery may yield greater outcomes of survival for those with localized PDAC

• Thanks to further insights into the molecular basis of PDAC, more treatments have been developed. Further personalization based upon an individual with PDAC may also yield better long-term outcomes.

Declaration of interest

E. Borazanci has served as a paid speaker for Ipsen; has serverd on advisory boards for Ipsen, Corcept, and Fujifilm; and has received institutional funding from Bristol-Myers Squibb, Pharmacyclics, Idera, Daiichi, Sankyo, Minneamrita Therapeutics, Ambry Genetics, Mabvax, Eli Lilly and Samumed. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.