Overall Survival, PFS Data Reported for Apalutamide in Non-metastatic CRPC at ESMO

Apalutamide (Erleada), a next-generation androgen receptor, along with ongoing androgen deprivation therapy (ADT), demonstrated an overall survival (OS) benefit compared with a placebo regimen in patients with non-metastatic castration-resistant prostate cancer (CRPC), according to new data reported at the ESMO Congress 2019 held in Barcelona, Spain.

The data, which are from the phase 3 SPARTAN study, further support apalutamide as a standard of care option in this population, according to lead study author Matthew R. Smith, MD, PhD, director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center.

For the study, patients with non-metastatic CRPC and prostate-specific antigen doubling time of ≤10 months were randomized to receive either apalutamide or a placebo, in combination with ongoing ADT. Previously, the primary analysis for metastasis-free survival showed an improved OS (HR, 0.70; 95% CI, 0.47-1.04; p = 0.07) and time to initiation of cytotoxic chemotherapy; however, OS results were immature at this point.

In a second interim analysis (IA2), updated data were reported for OS after 285 events, or 65% of required final events. The effects of apalutamide on chemotherapy, PFS2, and safety were also observed.

Based on the new analysis, apalutamide was associated with improved OS compared with placebo at 41 months of follow-up. Median OS was not reached in either arm, favoring apalutamide. However, these data were not found to be statistically significant. The updated analyses also demonstrated that 4-year OS rates for apalutamide and placebo were 72.1% and 64.7%, respectively.

Prior to the IA2, the study authors reported that 76 non-progressing patients in the placebo arm crossed over to open-label apalutamide. At IA2, the proportion of patients who received subsequent life-prolonging therapy was 69% in the placebo group and 40% in the apalutamide group.

Overall, updated results showed that apalutamide was associated with a 25% reduction in risk of death compared with placebo, which was observed despite the crossover of placebo patients to the apalutamide group. The effect on OS was also seen across patient subgroups, especially in those older than 65 years of age, no prior radical prostatectomy or local radiation, prior bone-sparing therapy, and PSADT >6 months.

Following Smith’s presentation, invited discussant Karim Fizazi, MD, PhD, provided commentary on the new data. He noted that with a hazard ratio of 0.75, the OS data shows a very nonsignificant difference at this point.

“At this moment, we cannot say that apalutamide prolongs survival in this setting,” Fizazi said. He said that more data on OS are to come; however, Fizazi explained that the PFS2 data showed a more meaningful clinical difference.

Reference

Smith MR, Saad F, Chowhurdy S, et al. 8430: Apalutamide (APA) and overall survival (OS) in patients (pts) with non-metastatic castration-resistant prostate cancer (nmCRPC): Updated results from phase III SPARTAN study. Presented at: ESMO Congress 2019. September 27-October 1, 2019. Barcelona, Spain.