Richard (Rick) JaeBong Lee, MD, PhD, medical oncologist at Massachusetts General Hospital, and assistant professor of medicine at Harvard Medical School, highlights key takeaways from the phase III SPARTAN trial in nonmetastatic castration-resistant prostate cancer (M0CRPC).

For the trial, investigators evaluated the use of apalutamide (Erleada) compared with placebo in a very similar design as the phase III ARAMIS trial with darolutamide. This trial also enrolled patients who had N1 disease, so some patients had lymph nodes, says Lee. Results showed an improvement in metastasis-free survival (MFS) of about 24 months. Specifically, MFS was 40 months with apalutamide versus 16 months with placebo.

A distinguishing feature of the trial was that patients who received either placebo or apalutamide were offered to receive abiraterone acetate (Zytiga) and prednisone at time of progression, he adds. Investigators also looked at another exploratory endpoint referred to as progression-free survival (PFS)2, which was defined as the time from randomization to progression on the second-line therapy, explains Lee. In terms of PFS2, patients randomized to apalutamide still had a benefit compared with those who received placebo and then went on to receive a second therapy, which was abiraterone for most patients.

The reason this is interesting is because some have argued that perhaps these drugs that are given in this space—which didn’t have any FDA approved therapies&mdash;may not necessarily impact the overall survival (OS) or the overall care for these patients, Lee says. However, what was seen by sustaining PFS2 is that the benefit from apalutamide may still be seen in the patients even when they’re given subsequent therapies. Patients who received placebo don’t necessarily have a catch-up in terms of their clinical benefit once they’re given an effective therapy after having received placebo. That’s important, says Lee.

As a field where several therapies have been shown to improve OS, and in other cancers as well, concepts like PFS2 are of particular interest, explains Lee, perhaps as another way to define how the different drugs are distinct from each other.

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Richard (Rick) JaeBong Lee, MD, PhD, medical oncologist at Massachusetts General Hospital, and assistant professor of medicine at Harvard Medical School, highlights key takeaways from the phase III SPARTAN trial in nonmetastatic castration-resistant prostate cancer.

Dr. Lee Highlights Key Takeaways From SPARTAN Trial in M0CRPC

Richard (Rick) JaeBong Lee, MD, PhD, medical oncologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, discusses the role of darolutamide in nonmetastatic castration-resistant prostate cancer (M0CRPC).

It is difficult to define darolutamide’s role in the prostate cancer paradigm, as apalutamide (Erleada) and enzalutamide (Xtandi) are 2 effective drugs that have already received FDA approval for use in this space. There is a lot of clinical experience with both of those drugs, says Lee. Whether or not darolutamide provides an improvement is difficult to know. All 3 drugs have demonstrated improvement metastasis-free survival, but there might be slight differences between them in terms of efficacy and safety profiles; these differences may help inform which agent to prescribe when they are all indicated in this setting. Other aspects that could be considered include the financial toxicity of these therapies; however, the cost of this category of drugs appears to be somewhat comparable with a similar impact for patients, adds Lee. As such, financial toxicity may not drive selection of the agent.

Dr. Lee on the Role of Darolutamide in M0CRPC

Richard (Rick) JaeBong Lee, MD, PhD, medical oncologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, discusses inclusion criteria of the phase III ARAMIS, SPARTAN, and PROSPER trials in nonmetastatic castration-resistant prostate cancer (M0CRPC).

In this space, there are 3 trials that have defined the way clinicians think about treatments, says Lee. Each trial that has come out, the ARAMIS trial for darolutamide, the SPARTAN trial for apalutamide (Erleada), and the PROSPER trial for enzalutamide (Xtandi), incorporated patients with M0CRPC. These are patients who have a prostate-specific antigen (PSA) doubling time that is less than 10 months. The 2 studies with apalutamide and darolutamide included patients who might have had nodal disease in the pelvis. Each trial randomized patients 2:1 and looked at metastasis-free survival, as assessed by PSA, as well as a bone scan and CT scan of the chest abdomen and pelvis every 16 weeks.

Additional inclusion criteria included negative scans with conventional imaging studies. One of the studies included at CT scan of the brain, but none of these included the more novel PET tracers that have become more widespread in practice due to their increased sensitivity, concludes Lee.

Dr. Lee on Inclusion Criteria of the ARAMIS, SPARTAN, and PROSPER Trials in M0CRPC

Richard (Rick) JaeBong Lee, MD, PhD, medical oncologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, discusses results from the phase III ARAMIS trial in nonmetastatic castration-resistant prostate cancer (M0CRPC).

In the trial, patients were given darolutamide, at 600 mg twice daily or placebo. Patients were blinded to their prostate-specific antigen values. Investigators assessed metastasis-free survival (MFS), defined as the identification of metastasis or death, whichever came first, says Lee. Investigators observed a median MFS of 40.4 months in the darolutamide arm versus 18.4 months in the placebo arm (HR, 0.41; 95% CI, 0.34-0.50; 

Other endpoints, including overall survival, also appeared to favor darolutamide although those data are premature. Regarding safety, the adverse events (AEs) observed with darolutamide did not seem to differ substantially from other agents. Patients who received the agent did not appear to have a statistically significant increase in AEs, such as fatigue, seizures, falls, and fractures, which have been some AEs of interest in other trials, explains Lee. In February 2019, a new drug application was filed for darolutamide for use in this setting, although it has yet to receive regulatory approval.

Richard JaeBong Lee, MD, PhD

Articles

Dr. Lee Highlights Key Takeaways From SPARTAN Trial in M0CRPC

Dr. Lee on the Role of Darolutamide in M0CRPC

Dr. Lee on Inclusion Criteria of the ARAMIS, SPARTAN, and PROSPER Trials in M0CRPC

Dr. Lee on the ARAMIS Trial in M0CRPC