Safety considerations with new treatment regimens for anal cancer

ABSTRACT

Introduction: Anal cancer is a rare malignancy, but incidence rates are rising. Primary chemoradiation is the standard of care for early disease with surgery reserved for salvage. Despite success in terms of survival, patients suffer significant morbidity. Research is underway to advance the field and improve outcomes for these patients.

Areas covered: This review aims to discuss the safety and efficacy of new approaches to treat anal cancer. A literature search was performed from January 1950 through November 2020 via PubMed and ClinicalTrials.gov databases to obtain data from ongoing or published studies examining new regimens for the treatment of anal cancers. Pertinent topics covered include miniature drug conjugates, epidermal growth factor receptor inhibitors, checkpoint inhibitor combinations, and novel immunomodulators.

Expert opinion: Based on emerging clinical data, the treatment paradigm for anal cancer is likely to shift in the upcoming years. One of the largest areas of investigation is the field of immunotherapy, which may emerge as an integral component of anal cancer for all treatment settings.

KEYWORDS:

• Anal cancer
• HPV
• immunotherapy
• oncolytic vaccine
• safety
• SCCA

Article highlights

• The landscape of anal cancer treatment has remained largely the same over the past few decades due to the rarity of this disease and paucity of randomized clinical trials

• Based on emerging clinical data, immunotherapy will likely develop an expanded role in the treatment of anal cancer

• For localized disease, PD-1 inhibitors are being evaluated in combination with, or after chemoradiation in order to induce longer sustained remissions

• For first-line metastatic disease, nivolumab and retifanlimab are being evaluated in combination with carboplatin and paclitaxel to see if the addition of PD-1 inhibition improves PFS versus chemotherapy alone

• For relapsed or refractory metastatic disease, investigation of multiple novel immunomodulators is underway, including bispecific proteins, oncolytic vaccines, and CAR-T cell therapy

This box summarizes key points contained in the article.

Declaration of interest

C Eng serves on advisory boards for Foundation of Medicine, Merck and Pfizer. C Eng is a consultant for HalioDx and Apexigen. T Geiger is a consultant for INX medical. KK Ciombor is a consultant for Merck. KK Ciombor receives institutional research funding from Pfizer, BMS, Array, Incyte, Daiichi Sankyo, Nucana, Merck, and Calithera. 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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.