Targeted drugs in combination with radiotherapy for the treatment of solid tumors: current state and future developments

Abstract

The continuously rising use of novel drugs, especially of molecules belonging to the group of targeted drugs is now shaping the therapeutic landscape. However, treatment combinations of targeted drugs with radiotherapy are still rare. Only the monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of locally advanced squamous cell cancer of the head and neck in combination with radiotherapy. Several targeted compounds are in advanced stages of clinical development for combination treatments with radiotherapy, of which substances with either anti-EGFR or anti-angiogenic mechanisms, such as trastuzumab, panitumumab, erlotinib, cilengitide and bevacizumab are the most promising. Aim of this article is to provide, mainly from a radio-oncological point of view, an overview about the current state as well as to give an outlook on the near future of the most advanced targeted combined treatment concepts for solid tumors.

Keywords::

• clinical study
• radiation oncology
• solid tumor
• targeted drugs

Financial & competing interests disclosure

E Selzer is on the scientific advisory board for Merck GmbH Austria and receives research funding from them. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Currently, only one targeted drug – cetuximab – is approved for treatment in combination with radiotherapy (RT).

• • Apart from cetuximab, trastuzumab, panitumumab, erlotinib and bevacizumab are the most promising compounds that may be approved in the near future for use in combination with RT.

• • From a current point of view, key biological mechanisms to target are EGF receptor (EGFR)-dependent signaling processes and targets affecting neo-angiogenesis.

• • From the list of the US FDA approved targeted drugs in oncology, at least 29 are in advanced clinical trials in combination with RT (Phase II or higher) and may therefore be regarded as potential candidates for approval within the next decade. The parallel development of relevant biomarkers useful in combination therapy will be a key issue. Potential biomarkers of interest for both radiation therapy and targeted drug therapy are, among others, EGFR genotype and EGFR protein expression levels, EGFR-dependent signaling cascades (e.g., MAPK, AKT), HPV/p16 expression, MGMT-methylation state and the mutation state of signaling molecules such as RAS, B-RAF as well as TP53 mutations and expression status and factors related to tumor hypoxia.

Notes