The OPTIMA trial set out to identify a group of patients with ER+/HER2- breast cancer normally treated with chemotherapy following surgery for primary disease, so adjuvant chemotherapy, who don’t actually gain any benefit from this treatment and so could avoid a toxic and unpleasant experience.
Could you outline the methodology?
This was a randomised clinical trial. What we measured in patients was recurrence of breast cancer. So we randomised 4,429 patients between two arms. The standard treatment arm was chemotherapy followed by endocrine therapy, chemoendocrine therapy, and the experimental arm was a test-directed arm. So all patients had a Prosigna test performed on their tumour and those with a Prosigna risk of recurrence, or ROR, score greater than 60 were assigned the same chemoendocrine therapy as patients in the control arm. Patients with an ROR score of under 60 were treated with endocrine therapy alone.
The trial was designed to show that the difference between recurrence rate in the two arms was 3% at most. So that was the non-inferiority margin and we consulted patients and clinicians about whether or not that was acceptable. We also performed a second analysis in the group of patients with low ROR score tumours. So in the control arm they all had chemoendocrine therapy anyway but in the test-directed arm these were the patients who received endocrine therapy alone. So that is an effect of randomisation between chemoendocrine therapy, standard of care, and endocrine therapy.
What did you find?
That’s simple, no difference. There was no difference in the risk of recurrence at five years between either the full trial population or the population of patients with low ROR score tumours. The trial met its predefined non-inferiority margins, with p-values of 0.006 and 0.003. If you look at the data slightly differently, we could say we were uncertain whether anybody benefitted from chemotherapy at all but if they did, at most two out of every hundred patients treated with chemotherapy avoided a recurrence as a result of that.
What impact could these findings have?
There were two groups where this finding was completely new. The first was we recruited premenopausal women down to a lower age limit of 40. Those women who were treated with chemotherapy and ovarian function suppression were no different to those who were treated with chemoendocrine therapy in the control arm. We also looked at patients with up to nine involved lymph nodes. So previously there’s been data with other tests up to three lymph nodes but the finding for up to nine lymph nodes is new.
We think this will all result in a change in the guidelines and a shift in the way that breast cancer is now treated.
