A “soft” chemotherapy combined with a targeted treatment has been found to be effective among older patients with an aggressive type of breast cancer.
A trial by scientists at the European Organisation for Research and Treatment of Cancer (EORTC) investigated treatments that reduce the toxicity levels associated with chemotherapy but have maximum effectiveness.
Professor Hans Wildiers, a medical oncologist from the University Hospital Leuven, Belgium, and colleagues from Italy, the UK, Portugal, and France, found that combining a ‘soft’ chemotherapy with antiHER2 therapy is highly active and has low toxicity for older patients with HER2 positive metastatic breast cancer.
The team recruited 80 patients – median age of 76.7 years – to the trial, who were randomly prescribed the targeted therapies trastumuzab and pertuzumab (TP) or to TP plus metronomic oral cyclophosphamide (TPM).
Prof Wildiers said that docetaxel combined with TP is effective in younger patients with HER2 positive metastatic breast cancer, but that it can be very toxic. This affects quality of life, especially in older women, which is an important consideration when used for palliation.
“We therefore decided to study whether combining TP with the ‘softer’ chemotherapy metronomic oral cyclophosphamide, would be active and have less toxicity than when used with docetaxel, or whether we could even omit chemotherapy and only administer TP in this age group,” he said.
“If tumour progression occurred after TPM or TP, patients would be eligible to receive another targeted drug, T-DM1, which is also generally well tolerated.”
Writing in The Lancet Oncology, the research team say that the found the TPM regime gave seven months longer progression-free survival compared with TP alone.
T-DM1 was also active, with a median disease control period of six months, after TPM or TP. Toxicity for all regimens was very acceptable in this frail population, with nine out of the 29 deaths during the study period not being breast cancer-related.
Professor Wildiers described the findings as “encouraging” because the gentler therapy delayed tumour growth in a significant proportion of frail patients for long periods.
“Our study also indicates that TPM and T-DM1 allow us to delay, or even avoid entirely, more toxic chemotherapy like docetaxel in these patients,” he said.
“In this age group, maintenance of QoL <quality of life> and the avoidance of toxic side-effects may be just as important as survival. We believe that there is a strong case for carrying out trials designed specifically for older people.”
The researchers write that frailty measurements should be included in future trials and that new drugs should also be evaluated in frail older people.
Dr Denis Lacombe, EORTC director general, said: “These impressive results underline how important it is to investigate drug efficacy and tolerance in older patients. Older people, particularly those who are frail, are a special case in exactly the same way as children are. We cannot and must not assume that because a drug is effective and relatively free of side effects in young to middle-aged adults that it will be the same for the elderly.”
Wildiers H, Tryfonidis K, Dal Largo L et al. Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer (EORTC 75111-10114): an open-label, randomised, phase 2 trial from the Elderly Task Force/Breast Cancer Group. The Lancet Oncology 10 February 2018; doi: 10.1016/S1470-2045(18)30083-4
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