The SPARTAN Trial Interim Analysis

Transcript: Elizabeth Heath, MD: I think they’re all in that same space of maturity. The apalutamide and enzalutamide data were reported in 2018, and then the darolutamide data were reported in 2019. So there’s nothing here that’s 5 years out. They’re all going to progress, and we’ll see little snippets of data get reported. As long as all that data are maturing and, in some sense, kind of having the same output, we’re pretty confident that class of drugs in this particular space is working.

Matthew R. Smith, MD, PhD: In contrast to the other 2 trials, ARAMIS and PROSPER, that evaluated other agents in nonmetastatic castration-resistant prostate cancer [CRPC], SPARTAN arguably provides the most comprehensive information by having this detailed set of secondary end points, some of which were late events that would be expected to follow development of metastasis by many months or, in some cases, years. We also made special efforts to increase the generalization of our results in SPARTAN, and that really involved 2 things.

One is the study evidence of improvement in metastasis-free survival [MFS]. The study was unblinded, and patients in the placebo arm were allowed to cross over to apalutamide. Second, a very high rate of patients went on to subsequent life-prolonging therapies. We encouraged that in the study design by providing abiraterone acetate to patients once they met the primary study end point. About 70% of patients in the placebo group went on to receive subsequent therapy—most of that abiraterone acetate plus prednisone. And so even with this relatively high rate of patient crossover to active agent, a very high rate of subsequent life-prolonging therapy, we see these consistent benefits and late clinical outcomes, including time to symptomatic progression, PFS2 [progression-free survival 2], and now with the updated data, this very strong trend in favor of better overall survival.

Elizabeth Heath, MD: I’m not sure if it will affect it. I think the original data set does enough to affect it. What you see is, in some sense, a possibility to have a patient be selected for a particular compound, because they have different adverse-effect profiles. The nice part is we actually have an opportunity to have the selection of agents. In a space that we really didn’t have much until recently, that’s a pretty important advancement.

Matthew R. Smith, MD, PhD: Collectively, the data from SPARTAN provide compelling evidence of clinical benefit. The impact on metastasis-free survival was large, with the reduction risk of 72%; and the effects were consistent across all subgroups. Furthermore, there is strong supportive evidence from secondary and exploratory end points that intervention with apalutamide improves clinical outcome. This includes an improvement in time to symptomatic progression and a strong trend in overall survival. The PFS2 data provide additional evidence that there is a late benefit of early initiation of apalutamide.

Alicia Morgans, MD, MPH: The latest analysis of SPARTAN was really interesting in that it got us closer to seeing that there might be an overall survival benefit to treatment. That is not quite statistically significant at this point, but the trend is extremely strong that it will get there. It’s probable that treatment of nonmetastatic CRPC patients with apalutamide will be associated with an overall survival benefit, and we eagerly look forward to having that data analysis in the future so we can see that it’s truly so.

Matthew R. Smith, MD, PhD: In this updated analysis of SPARTAN, we have substantially longer follow-up—41-month median follow-up compared with 20 months at the time of the primary metastasis-free survival analysis. At the time of this analysis, the median treatment duration with apalutamide was about 31 months, compared with 11 months for placebo. With this longer follow-up, we see a very similar safety profile for apalutamide compared with that previously reported in the primary MFS analysis. That includes rates of any adverse events—grade 3 or 4 adverse events, serious adverse events, and adverse events leading to treatment discontinuation. Notably, though, the reason for discontinuation due to disease progression was only 34% in the apalutamide group, compared with 74% in the placebo group.

Nonmetastatic castration-resistant prostate cancer is an important disease state, and I think we all now recognize that most men in this disease state go on to die of their cancer. We can now impact their clinical course by use of 1 of these agents—either apalutamide, enzalutamide, or darolutamide. I think that’s a very important and meaningful advance in the field.

Transcript Edited for Clarity