Emerging agents for metastatic pancreatic cancer: spotlight on early phase clinical trials

ABSTRACT

Introduction

Despite the recent development of new chemotherapeutic regimens and combination strategies, metastatic pancreatic cancer (mPC) still shows only a modest response to conventional cytotoxic agents. However, several novel therapeutic agents targeting the unique features of mPC are showing promise in clinical trials.

Area covered

This article reviews the current state of development of new agents targeting various systems and molecular pathways. We searched PubMed and clinicaltrials.gov in September 2021 with a special focus on ongoing early phase clinical trials to identify the promising therapeutic strategies for mPC.

Expert opinion

Extensive tumor heterogeneity, complex tumor microenvironment, genetic alterations of the oncogenic signaling pathways, metabolic dysregulation, and a low immunogenicity are hurdles for current treatment approaches. Ongoing research efforts strive to overcome these hurdles and are showing some promising early results.

KEYWORDS:

• Pancreatic cancer
• clinical trials
• targeted therapy
• immune checkpoint inhibitors
• antibody drug conjugates

Acknowledgments

Ian Chau would like to thank National Health Service funding to the National Institute for Health Research Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, UK.

Article highlights

• PARP inhibitors present a potential effective treatment option for patients with BRCA-associated PC.

• Mutated KRAS has therapeutic implications, especially when combined with targeting the MEK-ERK, PI3K, or metabolic pathways.

• Various approaches targeting molecular and metabolic pathways have shown encouraging early results for PC and multiple targeted approaches are also under clinical investigation as potentially effective regimens.

• The efficacy of combined immunomodulatory strategies including several ICIs is being investigated to enable the use of immunotherapies for PC.

• Personalized treatment based on molecular research and precision initiatives to facilitate precise patient selection may increase the clinical benefits of novel agents for PC.

Declaration of interest

I Chau would like to declare the following: Advisory Board: Eli-Lilly, Bristol Meyers Squibb, MSD, Bayer, Roche, Merck-Serono, Five Prime Therapeutics, Astra-Zeneca, OncXerna, Pierre Fabre, Boehringer Ingelheim, Incyte, Astella, GSK, Sotio, Eisai; Research funding: Eli-Lilly, Janssen-Cilag. Honorarium: Eli-Lilly, Eisai. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.