Medicine Matters oncology

My name is Boris Hadaschik. I'm one of the co-authors of the data being presented. I've been involved in the SPARTAN trial as part of the steering committee for the last couple of years, and that has been a pleasure. So this year at ASCO, we will report the final analysis for overall survival of the SPARTAN trial. And we are very happy that the SPARTAN trial has resulted, despite nearly 20% of crossover, in a significant prolongation of overall survival.

So while, in 2018, we have demonstrated that the addition of a apalutamide to ADT in men with nonmetastatic castration-resistant prostate cancer on conventional imaging has prolonged metastasis-free survival by two years, now, we can show in the final analysis that this early treatment really translates into an overall survival benefit of 14 months. This overall survival benefit is mirrored by the prolongation of progression-free survival, too, by apalutamide, which is also over one year. So it clearly shows us that early treatment makes sense in prostate cancer, and especially, in this situation of nonmetastatic castration-resistant disease.

What do these results mean for patients?

So these findings and the findings of the other two partner trials, PROSPER and ARAMIS, have set a new standard of care. And this new standard of care is that men with nonmetastatic castration-resistant prostate cancer should receive treatment with either apalutamide, enzalutamide, or darolutamide. And this treatment-- all survivor data were presented at ASCO-- is prolonging survival. And at the same time, it has no relevant detrimental effect on the quality of life of these men because in parallel to the harder oncologic data, there have been publications to show that despite adding another treatment and despite some financial toxicity, the quality of life of these initially asymptomatic men is not negatively affected.

How will physicians choose between these two agents?

I know that you would ask this question. It is really difficult because at this point in time, while we are filming this interview, they have no further publications being released on the three studies. So I have not had a chance to look at all details.

In the end, I think the mechanism of action of all three drugs is very similar. All three drugs are working. Then it depends on your healthcare context-- what you can prescribe, what you cannot prescribe. So in Germany, for example, we [INAUDIBLE] prescribe apalutamide and enzalutamide. And darolutamide has just yet gained approval. So I have no personal experience with darolutamide.

Looking at the data of the three phase-3 trials, you certainly notice that there are some variations with regards to adverse effects, but also, with regards to monitoring of the adverse effects. So it really depends. I think all three drugs are tolerated well, but they have their specifics.

So for example, with the drug I have been involved in, apalutamide, we certainly know that there is rash in patients, but this rash is rarely a significant problem. Darolutamide-- as I said, I have no personal experience-- it looks very promising, especially for frail patients because it does not cross the blood-brain barrier. But in the end, I think it will be a very hard decision to choose, and I'm looking forward to be able to prescribe all three of the drugs to gain personal experience.

And I think cost will be the same for all three drugs, so it's a good opportunity. It's a chance, and I really don't worry. And I do not want to give one specific recommendation because I think there's no data to back that up.

Would head-to-head comparisons be useful?

It is a difficult question. I think head-to-head comparisons in this disease space of nonmetastatic or M0 CRPC will not be undertaken because it just takes too long to observe these men. I think it may be interesting, for example, in neoadjuvant trials, where you have a biologic readout very soon. But to be honest, you have three different companies involved.

The mechanism of action of the three drugs is not that different. I think there are, academically speaking, more relevant problems that we need to solve. And I personally would not see a big need for head-to-head comparisons. I think all three drugs are good, and I'm not expecting any big trials.

The main message is we have three great drugs. They all prolong survival. And it's an opportunity or a privilege for physicians and the patients to be able to discuss all three drugs and then choose whatever you want to.