Experimental drugs for fallopian cancer: promising agents in the clinical trials and key stumbling blocks for researchers

ABSTRACT

Introduction

Fallopian tube carcinoma (FC) as a single entity is a rare disease. Although its diagnosis is increasing thanks to the widespread use of prophylactic salpingectomy, there are no clinical trials exclusively designed for FC.

Areas Covered

This review aims at identifying the most promising trials and future therapeutic pathways in the setting of FC.

Expert Opinion

Hot topics in FC treatment include the consequences of using PARP inhibitors (PARPi) as first-line therapy, ways to overcome platinum resistance, and the role of immunotherapy. Patient selection is a key point for future development of target therapies. Next-generation sequencing (NGS) is one of the most investigated technologies both for drug discovery and identification of reverse mutations, involved in resistance to PARPi and platinum. New, promising molecular targets are emerging. Notwithstanding the disappointing outcomes when used by itself, immunotherapy in FC treatment could still have a role in combination with other agents, exploiting synergistic effects at the molecular level. The development of cancer vaccines is currently hampered by the high variability of tumor neoantigens in FC. Genomic profiling could be a solution, allowing the synthesis of individualized vaccines.

KEYWORDS:

• Antibody drug conjugate
• immunotherapy
• MUC16 antibodies
• PARP inhibitors
• pelvic serous cancer
• platinum resistance
• target therapy
• tumor neoantigens
• vaccine
• WEE-1 inhibitors

Article highlights

• Fallopian tube carcinoma (FC) is thought to be the origin of 50–80% of high-grade serous carcinomas of the ovary or peritoneum, while it is rare as a single entity.

• Gold standard treatment of FC is cytoreductive surgery followed by systemic chemotherapy, using a combination of carboplatin and paclitaxel; maintenance with PARPi and/or bevacizumab has become a pillar of treatment in the last decades.

• Today, the development of platinum resistance and relapses after PARPi therapy are the main challenges in FC treatment. Moreover, the role of immunotherapy in FC treatment still needs to be clarified.

• New target agents alone or in combination with standard cytotoxic therapies are currently under investigation.

• Artificial intelligence and genomics could represent important tools for a more individualized and successful therapeutic pathway.

This box summarizes key points contained in the article.

Declarations of interest

The authors report the following disclosures: A Bergamini reports receiving consulting fees from GSK, Pharmamar, Clovis Oncology, Esai and MSD/Astrazeneca and travel support from GSK and MSD/Astrazeneca. Dr Giorgia Mangili reports receiving consulting fees, lecture fees, and travel support from AstraZeneca, MSD, Clovis, Esai, GSK, and Tesaro.

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 is reported. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed membership of the following scientific advisory boards: AstraZeneca, Eisai, GSK Inc., ImmunoGen Inc., Merck & Co., Mersana, Novacure, Roche Pharma, Sutro Biopharma, Vascular Biogenics Ltd and has received research funding from: Array BioPharma Inc., AstraZeneca., Eisai Inc., Genentech, Inc., Regeneron, Sanofi-Aventis US LLC, Tesaro Inc., Vascular Biogenics Ltd.

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

Additional information

Funding

This paper was not funded.