The decision to remove chemotherapy from treatment for women with HER2 positive breast cancer must be done on a personalised basis to identify which patients would benefit the most, a European conference has heard.
Delegates at the ESMO Breast Cancer Congress 2019, in Berlin, Germany, heard yesterday that the PERNETTA trial found that de-escalation in the first line treatment of HER2 positive metastatic breast cancer did not worsen two-year overall survival but significantly shortened progression-free survival.
It is why, said Dr Carmen Criscitiello, European Institute of Oncology, Milan, Italy, that personalised treatment is necessary.
"The introduction of anti-HER2 therapies has brought a huge survival benefit in early and advanced HER2 positive breast cancer, thus there is now a need for reducing the intensity and side effects of the treatment administered," she said.
"However, the priority is to identify which patients might be spared some toxic therapies without worsening the survival benefit."
The phase II trial involved 210 patients, who were randomly allocated either trastuzumab plus pertuzumab alone or trastuzumab plus pertuzumab combined with chemotherapy. Following progression, both groups received T-DM1 as second line therapy.
The researchers found that progression-free survival after first line therapy was 8.4 months with antibodies alone and 23.3 months with antibodies plus chemotherapy group.
At the conference, delegates were told that the results were similar regardless of hormone receptor status, and overall quality of life was also similar between groups during first line treatment.
The difference in progression-free survival between groups led the research team to look for predictive factors to identify patients who could receive targeted therapy alone with little or no detriment in progression-free survival. They used the PAM50 test to profile tumours of all patients in the trial.
Dr Criscitiello said it is important for studies in this field to select a specific population in which to attempt treatment intensity optimisation, admitting that using the PAM50 test to select patients with the HER2 enrichment subtype may be an effective approach.
"There was no biological selection of patients in the PERNETTA trial," she said. “Here we have a progression-free survival that is almost two times less than that achieved with chemotherapy. The short overall survival endpoint did not capture if denying a treatment, which is demonstrated to be meaningfully most effective, impacts on long-term survival. In addition, the sample size is very small to detect a difference in overall survival.
“Avoiding chemotherapy in HER2 positive disease is appealing for patients and investigators, but it has to be done safely."
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