PHARE trial results comparing 6 to 12 months of adjuvant trastuzumab in early breast cancer

New findings pose a question on optimal duration of trastuzumab therapy for women with HER2-positive early breast cancer; the subset analysis may give an answer

An academic randomised, non-inferiority trial conducted by the French National Cancer Institute (INCa) has compared a shorter trastuzumab exposure of 6 months versus the standard 12 months treatment. The PHARE trial addressed the question of duration of adjuvant treatment by trastuzumab in HER2-positive early breast cancer. The results are presented at Presidential Symposium of the ESMO 2012 Congress in Vienna.

More than 150 cancer care centres all over France participated, recruiting more than 3380 patients representative of the French population. The trial's primary objective was to compare 6 months versus 12 months of adjuvant trastuzumab therapy in terms of disease free-survival according to a non-inferiority schema.

The trial results are inconclusive for this non-inferiority hypothesis, according to Prof. Xavier Pivot, of the Université de Franche Comté, France, who presented the study results. Nevertheless, there is a trend in favour of 12 months treatment for the overall population and analysis of subgroups will be presented later in December.

The median follow-up in the trial was 42.5 months and at the time of the analysis 395 disease-free survival events were reported. According to the design of this trial, which allowed for a non-inferiority hazard ratio margin of 1.15, the 6-month trastuzumab arm (arm B) was not demonstrated to be significantly inferior to 12-month trastuzumab (arm A), since the confidence interval contains the 1.15 non inferiority margin (HR=1.28 (95%CI: 1.04 – 1.56, p = 0.29). However despite the inconclusive result in terms of non-inferiority, the HR of 1.28 suggests a trend favouring 12 months, according to the study researchers interpretation.

Further exploration of the data, especially in selected subgroups is ongoing; further results will be presented in a couple of months. The results probably won’t give a black and white answer, and the researchers will probably need to look at subsets of patients to see who benefits from six months of treatment and who should get a full year, Prof. Pivot concluded.

Commenting on the data, Prof. Christoph Zielinski, Chairman of the Clinical Division of Oncology, at Medical University Vienna, Austria, who was not involved in the study, noted that the progress in the treatment of patients with early breast cancer over-expressing HER2/neu was extremely impressive and particularly successful by the introduction of 1 year trastuzumab as adjuvant treatment. However, weighing benefit versus costs for the healthcare system is very important aspect, as the recurrence of disease in a patient leads not only to suffering and death, but also to an immensely increased burden for the society. The data from this study will add to the evidence how the latter aspects can be avoided by the delivery of an optimal duration of treatment for a selected patient population.