Dr Annabel Goodwin

A Cochrane systematic review has challenged the standard sequencing of neo-adjuvant treatment for early breast cancer with anthracycline-based chemotherapy first followed by a taxane.

The review, conducted by medical oncologists at Concord Hospital, Sydney, found equivalent outcomes for both sequences in which either taxane or anthracycline chemotherapy were delivered first in a neo-adjuvant setting.

However, while a taxane-first sequence might reduce the risk of requiring dose reductions  for taxanes, the available evidence was not yet strong enough to recommend a change from current  practice of using antracyclines first for neoadjuvant therapy, the reviewers concluded.

And in the adjuvant setting there was not enough evidence on overall survival and disease free survival to draw conclusions, they said.

The review undertaken by the Cochrane Breast Cancer Group led by Dr Milita Zaheed and Dr Annabel Goodwin analysed data from 1415 participants in five neo-adjuvant studies and four adjuvant studies.

In the neo-adjuvant studies there was high to low-certainty evidence of equivalent outcomes for a taxane-first sequence in terms of overall survival  (Hazard Ratio 0.80) and disease free survival (HR 0.84) compared to anthracycline first sequencing. There was also a trend favouring a taxane-first sequence in pathological complete response over anthracyclines (Relative Risk 1.15).

In two studies the taxane first regimen probably reduced the number of dose reductions compared to anthracyclines first regimen (RR 0.33). There was little difference in risk of grade 3-4 neutropenia or neurotoxicity when taxanes were given first.

The review authors noted that it was currently standard practice in most institutions to administer a regimen of anthracycline‐based chemotherapy followed by a taxane for women with early breast cancer.

“The reason for this established sequence appears to be historical rather than linked to outcomes. Anthracyclines were developed first and the benefit of anthracycline chemotherapy for early breast cancer was established prior to that of taxanes,” they wrote.

The full publication of results from a study that showed better outcomes with a taxane-first sequence on outcomes such as pathological complete response and overall survival would help answer the question of whether a change in sequencing practice was warranted, they added.

The results of a study involving HER2 positive patients is also awaited, they said.