The European School of Oncology and ESMO, the European Society for Medical Oncology hold a meeting every two years for guidelines, international consensus guidelines, for advanced breast cancer in Lisbon in Portugal. And I am a member of that panel; we have 44 breast cancer experts worldwide, we meet every two years in Lisbon in Portugal and we issue statements, guidelines, practical guidelines, for physicians in practice to use to take care of patients with advanced breast cancer. That meeting actually has breast cancer experts of all fields and also we have nurses and breast cancer advocates as well who are part of our panel.
We met in November in 2017 for ABC4 guidelines. We publish the guidelines usually in The Annals of Oncology and in The Breast, both journals, and we also tour the world giving lectures on those guidelines. It is important that physicians hear the science, all the scientific presentations, but very often the clinicians want guidance. There are no clinical trials for every particular patient so this is why those guidelines are important. Here at this breast cancer conference I presented a selection, summary, of those guidelines, general statements as well as patients who had oestrogen receptor positive, hormone receptor positive, as well as some on hormone receptor negative, HER2 negative and also HER2 positive and I will summarise a few of them for you.
For advanced breast cancer an important statement that we repeat that when the patient has hormone receptor positivity, HER2 negativity, usually we should start treatment with hormonal therapy unless the patient has what we call visceral crisis, which means that the patient has advanced disease in their lung, in their liver, that is causing lots of symptoms and abnormal blood tests. Otherwise if the patient has only two or three lesions in the lung or two or three lesions in the liver there is no need to jump to chemotherapy, hormonal therapy is usually easier, better tolerated, a much better quality of life for the patient. So we insist on that issue.
Now we say post-menopausal women should receive aromatase inhibitors or tamoxifen or fulvestrant hormonal therapy as first line and now the new data coming out, one of the most important advances in the treatment of breast cancer since trastuzumab for HER2 positive, is CR CDK4/6 inhibitors used in hormone receptor positive, HER2 negative patients with metastatic disease. So either we have palbociclib, ribociclib and now the abemaciclib as well; those three drugs we spoke about them, we think they are a very good and reasonable option up front first line for patients with metastatic breast cancer. There was recently a study at San Antonio using ribociclib in first line for premenopausal women so now we issued a statement at the ABC4 guidelines that CDK4/6 inhibitors are recommended, a good option, for treatment in first line for all patients, whether post-menopausal or pre-menopausal, provided that pre-menopausal women are given ovarian function suppression. So we suppress the production of oestrogens, usually the ovaries initially are the most important. So either we do LHRH analogue, these are drugs that suppress the production of oestrogen by the ovaries, or we do oophorectomy or radiation but radiation therapy is less effective to suppress the ovaries. So those are the options so nowadays we say we suppress the ovaries and we treat them like post-menopausal women and this is the option - CDK4/6 inhibitors plus tamoxifen or aromatase inhibitor with the CDK4/6 inhibitor and ovarian function suppression.
Now, if the patient progresses after the use of aromatase inhibitors or prior hormonal therapy then the option is a CDK4/6 inhibitor with fulvestrant which is a drug that degrades the oestrogen receptor. An important statement for research now, also, is that we recommend, ABC4 guidelines, we recommend that clinical trials for hormonal therapy for hormone receptor positive, HER2 negative breast cancer patients should also involve pre-menopausal women because young women are an important subset - lots of young women have breast cancer and may have metastatic breast cancer. So we should have the option of enrolling them with clinical trials, in clinical trials, and give them the treatment along with ovarian function suppression.
Another important expert opinion consensus statement is that CDK4/6 inhibitors should not be continued beyond progression. So if the patient has a progression on those drugs we do not continue them, the patient should be changed to a different treatment. Those drugs are very expensive and we do not have clinical trials that show that there is a benefit if you continue them. So if the patient progresses on CDK4/6 inhibitors now we don't continue it, we switch to a different treatment.
Have there been any significant guideline updates?
One important aspect is biosimilars. We spoke about biosimilars, drugs that are similar to the original drug, that we said that biosimilars should be… we are in favour of using biosimilars, we now have a biosimilar for trastuzumab and we have biosimilars for colony-stimulating factors. They should be strict, there should be pharmacological and clinical strict assessment and approval by agencies like EMA, the European EMA, or the American FDA or other very strict associations that they have been tested in terms of pharmacology, clinical efficacy and toxicity. We also recommended to the panel that those drugs, really the importance is financial because they reduce the cost therefore we think that they should be substantially less expensive than the original drugs.
What is important is to always recognise who is the patient who is a candidate for hormonal therapy that we can spare giving chemotherapy, we can delay the use of chemotherapy for a year or two, which is very good. Also it is important to know how to follow these patients and pre-empt side effects. Many of the drugs I spoke of are very well tolerated, some drugs like everolimus are not very well tolerated but we should have ways of pre-empting, assessing, checking the patient, following the patient and making sure if there is a toxicity that we can prevent, we do prevent, and if it happens we should treat it. Very important to make sure that the quality of life of the patient is improved.