Systematic review
Concurrent administration of anti-HER2 therapy and radiotherapy: Systematic review

https://doi.org/10.1016/j.radonc.2017.07.006Get rights and content

Abstract

Background: Over the past few years, anti-HER2 targeted therapies have proven to be a key treatment in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers, as well as gastrointestinal tract tumors and head and neck tumors. Anti-HER2 therapies administered alone or in combination with chemotherapy have been extensively studied, but only limited robust data are available concerning the safety and efficacy of anti-HER2 molecules in combination with radiotherapy. Methods: We searched on Medline, Embase and Cochrane databases the articles providing data on the concomitant association between the antiHER2 therapies used in clinical practice (trastuzumab, pertuzumab, lapatinib and T-DM1) with radiotherapy. The articles were selected according to their pre-clinical and clinical relevance. Results: The trastuzumab-irradiation combination is the most studied, with a focus on the cardiac toxicity. The combination of lapatinib-irradiation was particularly studied in the context of cerebral metastases of HER2-positive breast cancer. The data on pertuzumab and T-DM1 were poor and are mainly case reports. Conclusion: To date, reliable conclusions about the toxicity and/or efficacy of concomitant irradiation with anti-HER2 therapies are difficult to make due to the heterogeneity of the data in the literature and need to be confirmed on a larger scale and long term follow-up. Nevertheless, no serious adverse events are reported and the toxicity profile seems to be manageable.

Section snippets

Search strategy

For this review, pre-clinical and clinical studies were identified through literature searches conducted from to January 1987 to December 2016. The search was performed using the National Library of Medicine (PubMed/MEDLINE), Excerpta Medical Database (EMBASE) and Cochrane database and only English written studies were selected. A research was performed using the following keywords “radiotherapy”, “irradiation”, “radiation”, “concurrent”, “concomitant” combined successively with each anti-HER2

Overexpression HER2, a radioresistance factor

In preclinical studies in vivo and in vitro, it is clearly identified that HER2-overexpression is a factor of radioresistance in breast cancer [23], [24], [25], [26]. An exogenously increase in HER2 levels in the MCF7 breast cancer cell line (which normally expresses low levels of HER2) by transfection (MCF7HER2) caused increased resistance of the cells to ionizing with increased clonogenic survival after radiation [23]. This radioresistance mechanisms are probably not all explored and complex.

Conclusion

HER2-positive cells have been demonstrated to have a radioresistant phenotype. In the presence of trastuzumab, lapatinib and T-DM1, HER2-positive cells may develop increased sensitivity to radiation, which may result in a more potent antitumor effect.

The main clinical trials investigating the potential synergistic effect of anti-HER2 therapy and radiotherapy have focused on trastuzumab and lapatinib. Concerning the trastuzumab, the prospective trials assessing this combination in breast cancer

Competing interests

All authors declare no conflict of interest.

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