Breast cancer patients who combine targeted drugs with hormone therapy have an increased risk of severe side effects, a major European conference will be told today.
The research, which is being presented today at the Advanced Breast Cancer Fourth International Consensus Conference (ABC 4) in Lisbon, Portugal and is published in the new edition of Cancer Treatment Reviews, shows that combining drugs that target specific molecules important for cancer development and the hormones that are driving it leads to a significant increase in the risk of severe or life-threatening health problems.
However, medical oncologists Dr Matteo Lambertini, of the Institut Jules Bordet, in Brussels, Belgium, and Professor Samuel Martel from CISSS Montérégie Centre/Hôpital Charles-Lemoyne, Université de Sherbrooke in Québec, Canada, say that most of the side effects are treatable and potentially preventable.
While studies have shown that patients with advanced breast cancer live longer without disease progression if they take combination therapy, it was not known how it would affect side effects.
This study analysed data from 8,529 patients who had participated in 16 randomised controlled clinical trials up to July 2017. All had advanced hormone receptor-positive breast cancer and the trials investigated hormonal therapies given in combination with targeted drugs, such as CDK4/6, PI3K or mTOR inhibitors, and anti-HER2 agents.
Dr Lambertini said: “Our study showed that the addition of targeted agents to hormonal therapy is associated with a significantly higher risk of grade 3 or 4 adverse side effects overall, irrespective of the specific type of side effect.
“We also looked at grade 3 or 4 adverse events of particular interest, such as fatigue, rash, nausea, diarrhoea and liver enzyme elevation, as well as specific side effects by class of drug.”
They found that the use of anti-HER2 agents, CDK4/6 and PI3K inhibitors significantly increased the risk of grade 3 or 4 fatigue, but mTOR inhibitors did not. They also discovered that anti-HER2 agents, PI3K and mTOR inhibitors significantly increased the risk of grade 3 or 4 diarrhoea, while CDK4/6 inhibitors did not.
Their research established that CDK4/6 inhibitors increased the risk of grade 3 or 4 adverse side effects almost three-fold; PI3K inhibitors doubled the risk; mTOR inhibitors nearly doubled the risk; and anti-HER2 agents increased the risk 2.5-fold.
However, Dr Lambertini said their study focused only on adverse events registered in the different trials and not on patient-reported outcomes, which are a more accurate measure to determine the actual frequency, severity and real impact of anti-cancer treatment on patients’ quality of life.
“There are specific guidelines for the prevention and clinical management of side effects caused by targeted therapies,” he said. “For example, recently, the prophylactic use of an alcohol-free dexamethasone mouthwash has been shown to reduce the incidence and severity of sore and inflamed mouth in patients treated with everolimus and exemestane, and it is likely to be considered as a new standard of care.”
He added that doctors and patients should take into account the potential side effects when considering combination therapies.
“The results of our study can potentially serve as a basis for designing future trials of co-medications for preventing and treating these adverse events; such studies are to be considered a research priority as more patients are likely to be managed with these new treatments in the coming years,” he said.
Martel S. et al. Risk of adverse events with the addition of targeted agents to endocrine therapy in patients with hormone-receptor positive metastatic breast cancer: a systematic review and meta-analysis. Cancer Treatment Reviews 2017. 3 November 2017.
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