Biologics in rectal cancer

ABSTRACT

Introduction

Despite the use of multimodality therapy, locally advanced rectal cancer (LARC) still presents high rates of disease recurrence. Fluoropyrimidine-based chemotherapy concurrently with radiation therapy (RT) remains the cornerstone of neoadjuvant therapy of LARC, and novel therapies are urgently needed in order to improve the clinical outcomes.

Areas covered

We aim to summarize data from completed and ongoing clinical trials addressing the role of biological therapies, including monoclonal antibodies, immune checkpoint inhibitors (ICIs), antibody-drug conjugates, bispecific antibodies, and gene therapies in the systemic therapy of rectal cancer.

Expert opinion

Deeper understanding of the molecular biology of colorectal cancer (CRC) has allowed meaningful advances in the systemic therapy of metastatic disease in the past few years. The larger applicability of biological therapy in CRC, including genome-guided targeted therapy, antiangiogenics, and immunotherapy, gives us optimism for the personalized management of rectal cancer. Microsatellite instability (MSI) tumors have demonstrated high sensitivity to ICIs, and preliminary findings in the neoadjuvant setting of rectal cancer are promising. To date, antiangiogenic and anti-EGFR therapies in LARC have not demonstrated the same benefit seen in metastatic disease. The outstanding results accomplished by biomarker-guided therapy in metastatic CRC will guide future developments of biological therapy in LARC.

KEYWORDS:

• Antineoplastic agents
• angiogenesis inhibitors
• monoclonal antibodies
• immune checkpoint inhibitors
• immunoconjugates
• bispecific antibodies
• genic therapy
• precision medicine

Article highlights

• Despite presenting marked molecular heterogeneity, locally advanced rectal cancer (LARC) is still managed by the ‘one-size-fits-all’ approach, with fluoropyrimidine-based chemoradiotherapy.

• Monoclonal antibodies and targeted therapies with proven efficacy in metastatic disease have not yet been extensively investigated in LARC.

• Antibody-drug conjugates and bispecific antibodies have been preliminarily evaluated in metastatic colorectal cancer and may be largely explored in LARC.

• Immune checkpoint inhibitors have demonstrated encouraging efficacy in the neoadjuvant treatment of LARC with microsatellite instability.

• The incorporation of novel systemic therapies in the management of LARC is urgently needed in order to improve the clinical outcomes.

Declaration of interest

The authors have no 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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.