Young SIOG attendees and and the latest CDK inhibitors research in breast cancer

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Published: 22 Nov 2018
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Nicolò Battisti - The Royal Marsden NHS Foundation Trust, London, UK

Dr Nicolò Battisti speaks to ecancer at the International Society of Geriatric Oncology 2018 conference in Amsterdam about "Young SIOG" and the work this does.

He starts by introducing the project and explaining how it will also improve outreach and young people's engagement in geriatric oncology, particularly with respect to attendance at SIOG.

Secondly, Dr Battisti gives a thorough account of the current work he is affiliated with in London on breast cancer and CDK inhibitors.

This service has been kindly supported by an unrestricted grant from Janssen Oncology.

I have the honour to chair the Young SIOG group from this year, I took over from Dr Nienke de Glas who has been leading the group over the last couple of years. Essentially the Young SIOG group is a group of young clinicians and researchers from all over the world with a research or clinical interest in care for older cancer patients.
We are essentially leading on writing up a number of papers, review papers about a number of topics in oncology. We have our own sessions here at the SIOG conference, essentially we have our Young Assembly tomorrow, a Young SIOG poster work where essentially young members of the group earn the chance to present their own research. This year we also, after a successful session last year, we repeated a Young SIOG research session where essentially members of the group are allowed to present their own research project proposals to the geriatric oncology community. It was pretty good because obviously this is an excellent showcase for them, they can get input from the audience, from panellists, from senior members of the society and obviously improve their research proposals.

Is the young group attendance also growing for SIOG?

Yes it is. We are obviously also quite involved in organising also networking events just to catch up also outside a more formal context like this conference. For example, yesterday we had our networking dinner, the Young SIOG dinner, and we had an attendance of more than 40 attendees whereas last year there were thirty-something. So, yes, the young group is definitely gaining momentum and this is obviously thanks to the excellent work of who has been chairing this group for me and also thanks to the Board of the International Society of Geriatric Oncology which has always been very supportive.
It’s also a good way to engage people and engage people in geriatric oncology research, because obviously there is a huge lack of data out there to inform decision making in the care of older cancer patients.

Tell us about the work you do for the Breast Group in London on CDKs.

Obviously the approval, the marketing of CDK4/6 inhibitors has been one of the major breakthroughs in breast oncology over the last few years. There have been a number of trials that led to the approval of these drugs for the management of ER positive HER2 negative breast cancer in the metastatic setting, for example in the UK last year. We know that almost half of breast cancer patients are older, so above the age of 65, and we thought that it was important to review the data which is present out there to check whether enough older patients had been enrolled in those trials.
Essentially the Young SIOG group suggested essentially looking at this data and we are about to publish next week in the Therapeutic Advances in Medical Oncology journal a review of the use of CDK4/6 inhibitors in this setting, obviously in older patients. We have found that there’s a good proportion of older patients have been enrolled in the major pivotal clinical trials, essentially 45% in MONALEESA-2 which led to the approval of ribociclib in the first line setting; 36% in MONARCH 3 which led to the approval of abemaciclib in the first line setting; 39% of patients involved in the PALOMA-2 study were above the age of 65. So this is obviously good because it means that we have a good representation of older breast cancer patients in these pivotal trials but we also had a look in this review at outcomes, outcomes of this treatment in terms of efficacy, toxicity and quality of life.

The triallists, the authors of these trials, essentially have been presenting also age-specific data. We have a pooled analysis of the PALOMA studies testing obviously palbociclib which has shown essentially that efficacy outcomes are more or less the same as in the general PALOMA study populations, so a benefit in progression free survival up to 24 months which is valid also for older patients in the first line setting and up to 9-10 months in second line also for older patients.
Regarding ribociclib in the MONALEESA-2 study, again the efficacy in older patients is confirmed in first line; there are not much specific data published yet in second line in the MONALEESA-3 study. In the MONARCH 2 and 3 studies again the benefit is confirmed with abemaciclib also in older patients. The trouble is about toxicities, essentially. We do not have age specific data about toxicity published in the MONARCH 2 and 3 study populations; we do have data from the PALOMA studies, from this pooled analysis, saying that essentially it seems that palbociclib is tolerated pretty well also in the older population. Regarding MONALEESA there is probably a suggestion of some increased toxicities in terms of anaemia and fatigue but actually there haven’t been new major concerns about safety of these drugs.

Another very important endpoint in this setting is obviously also quality of life for older patients and here there is quite a big gap of data. Essentially we have a subset analysis from MONALEESA-2, so testing ribociclib, which is showing that quality of life is preserved in the older population. There is also probably an improvement in pain control, it was published this year, but other than that there are no data about quality of life and this is something that we should be really addressing.
So the question at this point is what to do, what drug do I need to use for the first and second line treatment of older breast cancer patients in the metastatic setting. We have three drugs, we know that efficacy is more or less the same as in younger patients, tolerance is fine. We don’t have much data about quality of life. Essentially I think we should be guided by a number of factors including obviously patient preferences, the schedule of the treatment – palbociclib, for example, requires patients to take one week off treatment every four weeks whereas other drugs are given continuously – and also the different side effect profiles. For example, with abemaciclib we have concerns about diarrhoea whereas for palbociclib there are concerns about myelosuppression. With ribociclib we are also required, at least in the UK, to monitor patients with repeat ECGs. So there is obviously room for making informed decisions and to try and treat the patient with the right drug.

There are trials going on at the moment, several about CDK4/6 inhibitors, in this review that is going to come up online in this journal next week. We have looked at clinicaltrials.gov and retrieved all the ongoing trials of CDK4/6 inhibitors that are given in different settings but we were quite concerned about the lack of geriatric assessments in these trials which is obviously very, very important in the older cancer patient population. Aging essentially makes people more heterogeneous so it’s important to assess very precisely each domain of our patients to make sure that we are making the right decision. We also need to bear in mind that there are patients who might be doing well anyway on just endocrine treatment without CDK4/6 inhibition. We have data from MONARCH 3 saying that, for example, patients with bony metastatic disease only are getting probably slimmer benefit from abemaciclib compared to patients with visceral disease, for example. So all these factors, considerations, need to be borne in mind in decision making. Certainly this gap of knowledge would be filled also by a proper screening for frailty and for those patients who screen positive a comprehensive geriatric assessment.
In this review at the end and in discussion of this review essentially we provided an algorithm, a hypothetical algorithm, to guide decision-making in first and subsequent lines of treatment. So if a patient is not deemed frail or vulnerable on screening then she should be treated as younger patients. If an older patient is found to have any vulnerabilities, if there is anything which is reversible through multidisciplinary interventions or rationalising concurrent medications or physiotherapy support, dietician input, then we can see if there’s anything reversible and then, at that point, if these patients are fit treat them as younger patients. If they are not then there is obviously the option of considering endocrine treatment alone without CDK4/6 inhibition which, again, is still a good treatment option especially in this setting.

It’s very, very important to consider also drug interactions with CDK4/6 inhibitors – there are antibiotics, commonly used anti-epileptics which may have obviously severe interaction with this drug. So it’s a complex management and probably CGA is the answer to guide decision making.