Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting.

Annalisa Pappalardo,Bruno Daniele,Luca Pompella,Emilio Francesco Giunta,Ferdinando De Vita,Piera Federico,Angelica Petrillo,Giuseppe Tirino

doi:10.3389/fonc.2021.695627

Annalisa Pappalardo, Bruno Daniele + Show 6 more

Open Access

https://doi.org/10.3389/fonc.2021.695627

Copy DOI

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite progresses in surgical and pharmacological treatment in recent years. High potential for metastases is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underlying pathological processes. However, nowadays research is focusing on the search for personalized approaches also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investigating new therapeutic targets. In this context, the aim of this narrative review is to summarize the current treatment scenario and new potential therapeutic approaches in early stage PDAC, from both a preclinical and clinical point of view. Additionally, the review examines the role of target therapies in localized PDAC and the influence of neoadjuvant treatments on survival outcomes.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is a candidate for the second leading cause of cancerrelated death in 2030, with a five-year survival rate of 5-7% [1]
PDAC treatment has hugely improved in recent decades
Even if the use of gemcitabine has been the better therapeutic chance for those patients for a long time, both in adjuvant and in metastatic settings, a lot of new drugs and strategies are appearing in therapeutic armamentarium today

Summary

INTRODUCTION

Pancreatic ductal adenocarcinoma (PDAC) is a candidate for the second leading cause of cancerrelated death in 2030, with a five-year survival rate of 5-7% [1]. One of the biggest challenges in early-stage malignant tumors is to assess individual prognosis more accurately, regarding risk of either local or distant relapse Stratification of these patients is important to avoid unnecessary adjuvant treatment in those who will not experience disease recurrence and to better tailor post-operative treatment – i.e. number and type of drugs administered or treatment duration – in those who have a high probability of micro-metastases. These patients showed alterations in genes like BRCA1, BRCA2, and PALB2, and the authors could demonstrate a clear clinical usefulness of a platinum-based chemotherapy, at least in two subjects, assuming a possible role of PARP inhibitors in this context Based on those preliminary results, the phase III POLO trial evaluated the efficacy of maintenance therapy with Olaparib (a PARP inhibitor) in germline BRCA1/2 mutated metastatic PDAC patients. Experimental arm NeoPancONE NCT04472910 [104] PROJECTION NCT04246203 [105] NCT01072981 (HyperAcute-Pancreas Immunotherapy) [106] DECIST NCT04157127 [107] NCT04117087 (Pooled Mutant KRAS-Targeted Long Peptide Vaccine) [108] NCT00733746 [109]

Observational III I I

Findings

CONCLUSIONS