Pharmacodynamics of current and emerging treatments for cervical cancer

ABSTRACT

Introduction: Beyond early stages of cervical cancer (1A₁, IA₂, IB_1, IIA₁,), locally advanced disease (IB₂, IIA₂, IIA2, IIB, IIIA, IIIB, IIIC, IVA) and advanced (metastatic, recurrent or persistent disease) patients require drug therapy either as radiosensitizer, adjuvant or as palliative systemic chemotherapy.

Areas covered: This review briefly discusses the achievements in treating cervical cancer.

Expert opinion: Two studies are ongoing to optimize treatment after radical hysterectomy. These studies compare chemoradiation versus radiation in intermediate-risk patients or increasing treatment intensity (chemoradiation plus adjuvant chemotherapy versus chemoradiation) for high-risk and locally advanced cervical cancer. Concerning advanced disease, bevacizumab increased median survival for only 3.5 months when added to a cisplatin-doublet. Although this increase is slightly superior to the 2.9 months gained with cisplatin topotecan versus cisplatin, (0.6 months of difference), the doublet plus bevacizumab is considered the standard of care. Recently, pembrolizumab became an alternative for advanced disease that progresses to first-line treatment. Beyond that, the number of phase II and phase III trials in advanced disease is limited but on the increase. HPV E6/E7 oncoproteins are the Achilles Heel of cervical cancer, and there is cautious optimism that antagonists of these oncoproteins will be further developed.

KEYWORDS:

• Advanced cervical cancer
• locally advanced cervical cancer
• chemoradiation
• chemotherapy
• E6/E7 oncogenes
• HPV
• checkpoint inhibitors
• novel cytotoxics
• radiosensitizers
• tyrosine kinase inhibitors

Article highlights

• Worldwide, cervical cancer remains the fourth cause of cancer incidence and mortality

• Two ongoing studies are aimed to optimize treatment in surgically treated early-stage intermediate-risk and high-risk using adjuvant radiation alone or adjuvant chemoradiation respectively

• In locally advanced disease, studies to determine the role of dose-dense neoadjuvant chemotherapy followed by chemoradiation, and adjuvant chemotherapy after radiation are in progress

• A chemotherapy doublet plus bevacizumab is the current standard of care for advanced disease

• Several ongoing phase III trials are testing immunotherapy added to chemotherapy as first-line and second-line treatment for advanced disease.

This box summarizes key points contained in the article.

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

A reviewer of this manuscript discloses being the Chief Scientific Officer of ISA Pharmaceuticals, a biotech company aiming at therapeutic cancer vaccines against High risk HPV and associated diseases. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.