Yes, this is significant that two out of four papers selected for a plenary session focus on breast cancer. One is the combined analysis of two large studies, TEXT and SOFT, investigating the role of aromatase inhibitors in pre-menopausal women. As you know, these compounds are used exclusively in post-menopausal women but here was the question whether this particular exemestane, one of the aromatase inhibitors, in combination with a LHRH analogue is better than the combination of the analogue with Tamoxifen which is considered in some parts of the world as standard therapy, standard endocrine therapy in this population.
And the answer?
The answer is that indeed this combination provides some benefit in terms of disease free survival compared with the standard therapy. This is not yet translated into overall survival benefit but the difference is in the range of 4% so it is notable and perhaps we should consider it, if confirmed in long-term follow-up, as a new standard.
What about the other plenary sessions?
The other important study, again an adjuvant study, was the study comparing standard adjuvant therapy in HER2 positive breast cancer patients, that is chemotherapy plus trastuzumab, versus the same in addition of lapatinib, another HER2 inhibiting agent. Despite very promising data from the NeoALLTO study where these combinations were tested in the neoadjuvant setting where the CR rate was doubled, this study is negative. That is, there is a small benefit from adding lapatinib to trastuzumab at the expense of much higher toxicity but most importantly there is no significant benefit from this combination.
And this is presumably more cost effective?
Yes, that saves a lot of extra cost and of course it keeps toxicity at the acceptable level. You have to remember that adjuvant therapy is continued for twelve months and, of course, it’s very essential to keep good quality of life during this time.
What about ovarian protection?
Indeed, a very interesting study showed that using a LHRH analogue during chemotherapy in pre-menopausal women increases the chance of fertility. It is not only translated into a higher rate of women keeping their pre-menopausal status but also in a higher rate of pregnancies which is, of course, the most important final endpoint.
What about immunological parameters?
This is still measuring genes because these are genes related to immunology, immune genes, I would say. Indeed, the signature of 14 of these genes were shown to be highly predictive for trastuzumab benefit in the adjuvant setting, namely the NICE study based on one of the large trastuzumab adjuvant studies investigated the role of these genes and the expression of these genes in primary tumours. The study showed that around half of patients with a particular signature have no benefit from trastuzumab therapy. So, in fact, again if confirmed in a validation study, even so, they did several internal validations, if confirmed probably half of patients may be spared trastuzumab or some other anti-HER2 therapy will be necessary to increase the benefit because there is absolutely no benefit from trastuzumab alone.
Doesn’t this seem quite an interesting angle to look at patients who may be spared from treatment?
It also shows a very important role of immunologic factors in this type of therapy. This is meant to be anti-HER2 therapy but probably there are also some other mechanisms, not only anti-HER2 action.