Neeraj Agarwal: Hi, my name is Dr. Neeraj Agarwal. I'm a professor of medicine and director of Genitourinary Oncology program at the Huntsman Cancer Institute, University of Utah. Today, we'd like to welcome Dr. Praful Ravi, faculty at the Dana-Farber Cancer Institute, who will be doing an oral presentation on exciting novel data from ICECaP database. So first of all, Praful, welcome.

Praful Ravi: Thank you for having me here. Pleasure to be here.

Neeraj Agarwal: And thanks for taking the time, and congratulations on your oral presentation at the ASCO 2025 meeting, where you will be talking about adding docetaxel to ADT plus hormonal therapy plus ADT plus radiation therapy in localized high-risk prostate cancer patients from ICECaP database. So why did you decide to pursue this study?

Praful Ravi: So as we all know, ADT, androgen deprivation plus radiotherapy is a standard of care in the treatment of high-risk localized disease. And recently, the addition of abiraterone to that was shown to be beneficial in the patients with the very high risk disease per the STAMPEDE criteria. Several trials have actually looked at adding docetaxel in the localized high-risk setting with ADT and radiotherapy, and the results have been generally mixed.

It's not an accepted standard of care. So we wanted to, A, perform an individual patient data meta-analysis, looking to see where the docetaxel is beneficial, and B, from ICECaP, we published work about a year ago, showing that patients with two to three high risk factors, so Gleason 8 or above, PSA greater than 20, clinical T3 or 4, and/or clinical node positive disease. They have the poorest outcomes with standard of care ADT plus radiotherapy. So we wanted to see, is there a population of patients in whom docetaxel might be beneficial?

Neeraj Agarwal: So how many patients are these?

Praful Ravi: So we had four randomized trials, GETUG, STAMPEDE, Dana-Farber trial, and a GETUG, STAMPEDE, DFCI. And one more I'm forgetting now. And it was 1,700 patients overall, of which 1/3 were classified as high risk, where we said only one risk factor and 2/3, about 1,000, were classified as very high risk, two to three high-risk factors, or node positive.

Neeraj Agarwal: And what were the findings?

Praful Ravi: So the overall population to the 1,700 patients we had individual patient data on, docetaxel did not lead to a statistically significant improvement in metastasis-free or overall survival. The hazard ratios were less than 1. P-value was not significant.

In terms of other endpoints, event-free survival, prostate cancer death, and time to metastasis, there actually was a modest and significant benefit for EFS event-free survival and prostate cancer death and not for time to metastasis. So overall, didn't seem to benefit, significantly.

When we looked at the very high risk patients, and compared to just the high risk patients, there was a trend towards greater benefit for docetaxel in the very high risk patients, meaning the hazard ratios for the high risk patient for MFS, OS, these other endpoints were around 0.9, 0.95 range, whereas for the very high risk patients it was around the 0.7, 0.8 range.

So there was a differential effect. The statistical interaction test was negative, meaning it wasn't significant in terms of interaction. But the summation is that there seems to be a greater benefit potentially in the very high risk patients.

Neeraj Agarwal: So moving forward, looks like we should have a trial looking at this very high risk localized prostate cancer to see whether docetaxel can help them.

Praful Ravi: That is a potential. I mean, I think it would be hard to accrue everyone with very localized high risk, maybe the very high risk patients themselves. We could look at that. In addition with ADT plus radiotherapy plus or minus ARPI. I know the PEACE group are doing a cabazitaxel study in the very high risk or the low high risk patients.

But could we maybe look at biomarker selection in that group to maybe really or do some biomarker work to find maybe is there a signature associated with benefit from docetaxel and really focus efforts into that particular group because these trials are going to take years to do. Many, many patients to show a benefit. So can we really find a subset? But that would be a natural extension to see. Is there a group in whom intensification beyond standard of care with docetaxel can benefit?

Neeraj Agarwal: This is definitely-- like, first of all, a great point. This is definitely an area of high unmet need. A vast majority of these patients are going to develop metastatic disease. So can we do something early on to prevent metastatic disease, the lethal form of disease, in these patients?

So first of all, again, congratulations. This is a really large number of patients, very useful information. And hopefully it will help us in better prognostication counseling and treatment selection for these patients, maybe design of future trials.

Praful Ravi: Exactly, that's what we hope it will lead to. Or at least promote further work. Looking at a relatively old drug like docetaxel, can we bring it into the current modern era in the localized setting.

Neeraj Agarwal: Very inexpensive drug.

Praful Ravi: Exactly, right.

Neeraj Agarwal: Yes, yes, well, thank you, Praful, for being here.

Praful Ravi: Thank you very much.