Ganesh V Raj, MD, PhD, presents data from the phase 3 SPARTAN trial of apalutamide for nonmetastatic castration-resistant prostate cancer (nmCRPC).
Jorge A. Garcia, MD, FACP: Let’s get into the data. Ganesh, if you don’t mind, speak on the SPARTAN data, which led to the FDA approval of apalutamide in the M0 [nonmetastatic) space.
Ganesh V Raj, MD, PhD: I’m going to present the SPARTAN trial, which is the trial that was initially presented at ASCO GU [the American Society of Clinical Oncology Genitourinary Cancers Symposium] and led to the approval of apalutamide for this space.
It’s a phase 3 clinical trial, and the eligibility criteria for this was nonmetastatic CRPC [castration-resistant prostate cancer] with patients who had no evidence of pelvic lymph nodes that were larger than 2 cm and PSA [prostate-specific antigen] doubling time of less than 10 months. These are eligibility criteria for entry into the trial. Twelve hundred patients were randomized 2:1, with 800 patients getting apalutamide and 400 patients getting placebo. The end point here was metastasis-free survival [MFS]. This is an end point that Dr Taplin, and Chris Sweeney, [MBBS,] know a great deal about because they’re the ones who spearheaded the development of MFS as an end point for prostate cancer. The patients were then followed until progression or death. At this point, after the study was released, they got a second treatment at the discretion of the treating physician, including open-label [abiraterone and] prednisone as a possible treatment.
If you look at the baseline characteristics of the 2 groups, it’s very similar between the apalutamide group and the placebo group; same median age, about 74, same PSA doubling time, about 4.5 months the median, and the vast majority of the patients had a PSA doubling time of less than 6 months. Remember, everyone had to be less than 10 months. So, 71% had PSA doubling time of less than 6 months in both groups, and the vast majority of them did not have a bone-sparing agent. A lot of them had either prostatectomy or primary radiation therapy as definitive local therapy to their prostate. There were equal numbers in both of the key parameters that could influence the outcome.
If you look at the outcome, it was a home run. It was a clear difference in metastasis-free survival between the placebo group, marked PBO, and the apalutamide group. The median metastasis-free survival in the placebo group was 16 months, and almost a 24-month improvement in survival in the apalutamide group with 40-month median metastasis-free survival. Overall, there was a 14-month difference in overall survival as well. If you are only interested in overall survival as an end point, even then the apalutamide met the criteria. Remember, a lot of these placebo groups were then allowed to randomize over or to be treated by antiandrogen therapy. But even then, the median survival there was 60 months versus 74 months in the apalutamide group. Overall, metastasis-free survival and overall survival versus placebo were both statistically significant end points.
In the M0 CRPC, the overall survival, if you look at the number of patients as you go further along, are fewer and fewer, but the overall improvement in survival is dramatically different with a P value of less than .05. The most frequent adverse effects were seen. Fatigue is a significant [adverse] effect in the patients treated with apalutamide versus placebo, 32% in the apalutamide plus ADT [androgen deprivation therapy] vs 21% in the placebo plus ADT, so it’s a significant increase in fatigue and significant increase in hypertension compared to placebo. However, most of these were lower grades. If you look at the actual grade 3 and 4, it’s 0.9% for fatigue, 0.3% for fatigue in their placebo group, and not much difference in the hypertension between the 2 groups or significant differences between the 2 groups in terms of adverse events that would basically block treatment.
Transcript edited for clarity.