Hello, I am Pierfranco Conte, I am a medical oncologist working in Padova, Italy, and I will present today a task of a ten-year update of the Short-HER randomised trial. This is a phase III non-inferiority trial comparing nine weeks of trastuzumab given with chemotherapy to the standard one year of trastuzumab plus chemotherapy. The patients eligible for the trial had to have either node positive disease or a node negative disease with a tumour size larger than 2cm plus at least one more risk factor, including grade 3, or HER2 hormone receptor status negativity, or Ki67 more than 20%, lymphovascular invasion present or younger than 35 years of age.
The trial, again, was comparing chemo plus ten weeks versus chemo plus one year of trastuzumab. Also, the two chemo regimens were different because the chemo in the short treatment arm consisted of six courses of chemotherapy while in the long treatment arm the classic four courses of chemotherapy. So there was also less chemotherapy in the short treatment arm.
The study was initially presented at ASCO in 2017. At that time the median follow-up was 5% and we couldn’t claim non-inferiority according to the frequentist approach because the upper limits of the confidence interval crossed 1.29 which was the predefined limit to claim non-inferiority. However, already at that time, according to a pre-planned Bayesian analysis, the probability that nine weeks were not inferior to one year was 78%.
Now at ASCO 2023 we present the second co-primary endpoint of the study which is overall survival and the updated disease free survival at ten years, according also to the nodal status – node negative, node 1-3 positive lymph nodes and four or more positive lymph nodes. The median follow-up is now nine years.
At ten years the disease free survival on the long treatment arm is 78%; the ten-year disease free survival on the short arm is 79%. The overall survival on the long treatment at ten years is 89%; for nine weeks it is 88%. The hazard ratio is 1.09 but again, unfortunately, the upper limit of confidence still crosses the predefined limit to claim for non-inferiority. Again, according to a pre-planned Bayesian analysis the probability that nine weeks are not inferior to one year is now 93.2%.
According to a subgroup analysis there is no difference across the two treatment arms according to age and the hormone receptor status, no difference for stage 1 and stage 2 disease, no difference for node negative and nodes from 1-3 positive lymph nodes. There is an advantage for one year of trastuzumab for patients with stage 3 disease and for patients with 4+ positive lymph nodes.
The clinical consequences of this study, of course, this doesn’t change the standard of care in Western countries and the US because we are not able to claim for non-inferiority. But there are two main clinical values in the study. First of all, if, for any reason, even in Europe and the US, a patient with node negative or with up to three positive lymph nodes has to stop trastuzumab early, because of maybe a decline in the left ventricular ejection fraction, or an [inaudible] disease, or simply lack of compliance, the physicians can be quite reassured by this data that this doesn’t compromise the outcome of the patient.
Even more important, I believe that these data might be extremely useful for the vast majority of women worldwide who cannot afford, mainly for economical reasons, the course of one year of trastuzumab. For many of these women probably nine weeks would be an affordable treatment and, by sure, also an effective treatment.