Investigational drugs for recurrent or primary advanced metastatic cervical cancer: what is in the clinical development pipeline?

ABSTRACT

Introduction

Recurrent or primary advanced metastatic cervical cancer (R/M CC) has a poor prognosis with a 5-year-survival rate of 16.5%, demanding novel and improved therapies for the treatment of these patients. The first-line standard of care for R/M CC now benefits from the addition of the immune checkpoint inhibitor, pembrolizumab, to platinum-based chemotherapy with paclitaxel and bevacizumab. Additionally, new options for second-line treatment have become available in recent years.

Areas covered

Here, we review current investigational drugs and discuss their relative targets, efficacies, and potential within the R/M CC treatment landscape. This review will focus on recently published data and key ongoing clinical trials in patients with R/M CC, covering multiple modes of action, including immunotherapies, antibody–drug conjugates, and tyrosine kinase inhibitors. We searched clinicaltrials.gov for ongoing trials and pubmed.ncbi.nih.gov for recently published trial data, as well as recent years’ proceedings from the annual conferences of the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO), and the International Gynecologic Cancer Society (IGCS).

Expert opinion

Therapeutics currently attracting attention include novel immune checkpoint inhibitors, therapeutic vaccinations, antibody–drug conjugates, such as tisotumab vedotin, tyrosine kinase inhibitors targeting HER2, and multitarget synergistic combinations.

KEYWORDS:

• Recurrent cervical cancer
• advanced metastatic cervical cancer
• investigational drugs
• immunotherapy
• antibody–drug conjugate
• tyrosine kinase inhibitor
• combination therapy

Article highlights

• Cervical cancer is the fourth most common female cancer, accounting for approximately 340,000 annual deaths

• There is an unmet clinical need in the second-line therapy of recurrent/metastatic cervical cancer as there are limited options and there is currently no accepted standard of care

• Recent approvals of cemiplimab by the EMA and tisotumab vedotin by the FDA are providing alternate therapies to the armamentarium, and results from ongoing combination trials are eagerly awaited

• Many other therapeutics of interest are emerging in the development pipeline including novel immune checkpoint inhibitors, tyrosine kinase inhibitors, and multitarget synergistic combinations

• Therapies with novel mechanisms of action are also emerging, such as antibody–drug conjugates (e.g. tisotumab vedotin) and therapeutic vaccination

This box summarizes key points contained in the article.

Acknowledgments

Medical writing support was provided by Meridian HealthComms Ltd, funded by Seagen.

Declaration of interests

I. Vergote (IV) receives consulting fees from Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology and Zentalis. I. Vergote performs contracted research (via KULeuven) for Oncoinvent AS. I. Vergote performs corporate sponsored research for Amgen and Roche. I. Vergote receives accommodation and travel expense remuneration from: Karyopharm, Genmab and Novocure.

I. Ray-Coquard receives consulting/advisory fees from PharmaMar, Merck Serono, Novartis, Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Mersana, MSD, Novocure, Novartis, OncXerna, Seagen and Verastem Oncology. I. Ray-Coquard receives travel/accommodation/expense remuneration from AstraZeneca, Clovis Oncology, PharmaMar, Roche, and Tesaro/GSK. IRC receives honoraria from AstraZeneca, Clovis Oncology, Genmab, Immunogen, Merck, Roche, and Tesaro/GSK. IRC receives research funding (to institution) from, BMS, MSD, and GSK.

D. Lorusso receives consulting/advisory fees from PharmaMar, Merck Serono and Novartis. D. Lorusso performs a speaker bureau role for AstraZeneca, Clovis Oncology, PharmaMar, and Tesaro/GSK. D. Lorusso receives travel/accommodation/expense remuneration from AstraZeneca, Clovis Oncology, PharmaMar, Roche, and Tesaro/GSK. D. Lorusso performs expert testimony on behalf of Clovis Oncology. D. Lorusso receives honoraria from AstraZeneca, Clovis Oncology, Genmab, Immunogen, Merck, Roche, and Tesaro/GSK. D. Lorusso receives research funding (to institution) from Clovis Oncology, Merck, PharmaMar, and Tesaro/GSK.

A. Oaknin receives renumeration for advisory boards from: Agenus, AstraZeneca, Clovis Oncology, Inc., Corcept Therapeutics, Deciphera Pharmaceutical, Eisai Europe Limited, EMD Serono, Inc., F. Hoffmann-La Roche, GlaxoSmithKline, GOG, Immunogen, Medison Pharma, Merck Sharp & Dohme de España, Mersana Therapeutics, Novocure GmbH, Pharma Mar, prIME Oncology, ROCHE FARMA, Sattucklabs and Sutro Biopharma, Inc. A. Oaknin receives accommodation/travel/expense renumeration from Roche, AstraZeneca, PharmaMar, GSK and Clovis.

D. Cibula serves as advisory board member for Akesobio, Astra Zeneca, GSK, MSD, Novocure, Roche, Seagen and Sotio.

T.Van Gorp performs a consulting or advisory role for; AstraZeneca, Eisai Europe, GSK, Immunogen, MSD, OncXerna Therapeutics, Seagen (all fees to institution). T.Van Gorp (receives travel/accommodation/expense renumeration from AstraZeneca, GSK, Immunogen, MSD and PharmaMar. TVG performs corporate sponsored research (via institution) for: Amgen, AstraZeneca and Roche.

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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

Seagen provided funding for medical writing assistance and covered the cost of the open access fee. There is no grant number associated with this funding. Seagen did not have any input into the content of the manuscript.