Gerhardt Attard, MD, on the interaction between Decipher score and docetaxel benefit

In this video, Gerhardt Attard, MD, PhD, FRCP, highlights the background and key findings from the study, “Decipher mRNA score for prediction of survival benefit from docetaxel at start of androgen deprivation therapy (ADT) for advanced prostate cancer (PC): An ancillary study of the STAMPEDE docetaxel trials,” (NCT00268476) which was presented at the 2024 European Society for Medical Oncology Annual Congress in Barcelona, Spain. Attard is a medical oncologist at University College London in the UK.

Video Transcript:

Patients with metastatic prostate cancer are now treated with intensified hormone treatment. So, they receive injections every 3 to 6 months, and then androgen receptor pathway inhibitors, and there are 4 or 5 that are used routinely. The outcomes for some are very good, and for some patients are not good. In fact, the natural history and prognosis is highly variable. As a community, we're looking at better ways to improve outcomes, and one way to achieve that, potentially, is docetaxel chemotherapy. We've never tested the question of randomizing patients receiving ADT and what we call an ARPI, androgen receptor pathway inhibitor, with docetaxel or no docetaxel, but many in the community believe docetaxel will improve patients' life expectancy. However, we also know with certainty that docetaxel impacts quality of life significantly within 16 months. But we've also shown in an analysis in STAMPEDE that after 18 months, that quality of life remains reduced. We have worked for about 7 or 8 years now to identify a predictive biomarker that identifies docetaxel-sensitive cancers. That could allow physicians to choose which patients would have intensified docetaxel chemotherapy and tilt the balance of benefits, or the balance in favor of potential benefits, outweighing the risks.

To do this, we have analyzed diagnostic tumor samples from just over 1500 patients who are randomized in 2 trials in the STAMPEDE platform protocol. Half of the patients were randomized ADT, ADT/abiraterone, and half were randomized––the hormone suppression is ADT––hormone suppression with or without docetaxel. Together with our partners at Veracyte, we generated expression values for all genes in the transcriptome. We then extracted a signature. In fact, we've extracted a number of signatures, and focused on 59. Before looking at the data we prespecified Decipher as a signature of interest for prediction of docetaxel effect. This is based on pilot data we generated in a training set in another trial called CHAARTED.

Today, we're presenting the results of this analysis, and we show that patients who have a high Decipher score derive significant benefit from docetaxel. The hazard ratio in that group is about 0.6. For patients in the low Decipher group, there's no evidence of benefit from docetaxel treatment; that hazard ratio is close to 1. We, probably for the first time, in the context of docetaxel chemotherapy, have a statistically significant interaction P value. What this means is that there is statistical certainty that the benefit of docetaxel differs by the Decipher test.

We currently are using metastatic volume, number of metastases on conventional scans, to make the decision on whether to treat someone with docetaxel or not. We show in an exploratory way that this greater effect with high Decipher is consistent regardless of metastatic volume. So, both in the high-volume patients and in the low-volume patients. The debate will now center on whether they should be implemented into clinical practice [over the] next week. Views will differ. Do we need to prospectively re-validate this in a large, randomized trial over the next 5 to 10 years, or can we use this data in isolation, potentially with other retrospective studies––and I've mentioned CHAARTED––to change our clinical practice? I think that's what we'll debate further over the next few weeks. My view is that this data is so strong we should be starting to act on it. But of course, there are nuances, and there are differences in access globally. There's a number of considerations to be made in that regard.

This transcription has been edited for clarity.