Tomorrow morning’s presentation is a pooled analysis of CDK 4/6 inhibitors, which is a class of drugs which has been approved for multiple uses in metastatic breast cancer in older women, focusing on women over 70.
What kind of pool are you pulling from then?
We basically looked at about five different registration trials, or studies which have come into the FDA, in the first line metastatic setting in combination with endocrine therapy.
Is that looking at any specific CDK inhibitors or just the whole family?
We looked at three different CDK 4/6 inhibitors but we pooled all the data, so de-identified each drug.
What are the findings that you’re reporting?
What we’re reporting is that it appears that older women, particularly women over 70 but we also looked at other age cut-offs like 75 and 80, appear to derive similar benefit from this class of drugs in terms of progression free survival as their younger counterparts. That’s for the efficacy portion. This is an exploratory analysis so it’s important to note that. We also looked at safety, and what we did see there was that in older women, especially those over 70, there seemed to be higher rates of discontinuations as well as dose modifications, suggesting that the older patients did need a little bit more assistance or modifications in terms of managing these medications.
And these were just single agents?
These were single agents along with endocrine therapy or aromatase inhibitors.
And they have pretty well-established tolerability for older patients already then?
No, this is the first time, to my knowledge, that the older group of patients has been looked at specifically. Since this is a relatively novel class of drugs, we don’t really have an idea as to how specifically older women tolerate these drugs.
And in terms of how that would affect treatment for broader populations, because we were at the SIOG conference for geriatrician oncology, however they spell it out in French, and they were talking about how much of a population boom there is for the older patients coming.
Absolutely. Can you tell us your thoughts on that?
Part of the reason that we did this study is because older women and men are under-represented on breast cancer trials. So specifically for breast cancer we know that up to 20% of women with new diagnoses of breast cancer are 75 and older but when we looked at the last ten years of registration trials, that means trials that lead up to the drug approval for breast cancer, only 4% of those patients were 75 and older. We know there’s this huge disparity, particularly with breast cancer, and the FDA, as well as other stakeholders, are trying to address this.
And in terms of what other people can do with this data, either in their practice or trial design, how would you like to see this going forwards?
Specifically for these drugs and for all new drugs I think it is a decision that the healthcare provider makes by looking at the patient in front of them. I hope that this is an adjunct for then to show that their older patients do derive similar clinical benefit, as it appears in our analysis, but that in terms of the toxicity they may need closer management. In general, we need much more data and more studies, and we need more older patients to be enrolled on clinical trials.
That covers my questions. Is there anything else that might come up that we haven’t talked about?
I would just like to highlight a few initiatives at the FDA that I think could potentially improve this issue of under-representation of older patients on clinical trials. One is the FDA, along with ASCO and Friends of Cancer Research, have in the last few years dedicated a lot of effort to something called modernising eligibility criteria. Basically, they’ve teamed together with a group of key stakeholders to look at eligibility criteria as they currently stand and try to address ways to make them more rational. There’s a few topics which they’ve honed in on which I think could really relate to older patients. One is organ dysfunction. What that means is, right now there are pretty stringent requirements form for example, kidney function, to enrol on a clinical trial, but do they make sense? If a drug, for example, is not renally excreted or metabolised by the kidney do you need such stringent requirements for creatinine? This is an eligibility criteria that often excludes older adults because the kidney function just worsens naturally with age.
Another one is prior malignancies - many protocols just have an exclusion criteria that does not allow prior malignancies within the last two to five years. But many older adults do have maybe minor skin cancers or, for example, a low-grade prostate cancer that would otherwise exclude them from the trial. I think by addressing these and taking a more rational approach to eligibility criteria we may see an uptick in older adults being able to enrol on these trials.
Another is patient-reported outcomes. The FDA is leading a huge effort to incorporate the patient voice into drug development, and I think for this study it could be strengthened by more data from patients in terms of how they’re actually tolerating the drug.