Improved Survival With Apalutamide in Castration-Resistant Prostate Cancer

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TAKE-HOME MESSAGE

•This report provides data from the second prespecified interim analysis of a trial comparing apalutamide with placebo among patients with high-risk nonmetastatic castration-resistant prostate cancer. Those treated with apalutamide had improved overall (HR, 0.75) and progression-free (HR, 0.55) survival at this second time point. This benefit was observed despite treatment of placebo patients with apalutamide.

•Apalutamide appears to reduce the risk for death of patients with nonmetastatic castration-resistant prostate cancer and might be a viable treatment option for this patient population in the future.

– Neil Majithia, MD

BACKGROUND

In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2).

METHODS

One thousand two hundred and seven patients with nmCRPC were randomized 2 : 1 to apalutamide (240 mg daily) or placebo. The primary end point of the study was MFS. Subsequent therapy for metastatic CRPC was permitted. When the primary end point was met, the study was unblinded. Patients receiving placebo who had not yet developed metastases were offered open-label apalutamide. At IA2, pre-specified analysis of OS was undertaken, using a group-sequential testing procedure with O'Brien-Fleming-type alpha spending function. Safety and second progression-free survival (PFS2) were assessed.

RESULTS

Median follow-up was 41 months. With 285 (67% of required) OS events, apalutamide was associated with an improved OS compared with placebo (HR 0.75; 95% CI 0.59-0.96; P = 0.0197), although the P-value did not cross the pre-specified O'Brien-Fleming boundary of 0.0121. Apalutamide improved PFS2 (HR 0.55; 95% CI 0.45-0.68). At IA2, 69% of placebo-treated and 40% of apalutamide-treated patients had received subsequent life-prolonging therapy for metastatic CRPC. No new safety signals were observed.

CONCLUSION

In patients with nmCRPC, apalutamide was associated with a 25% reduction in risk of death compared with placebo. This OS benefit was observed despite crossover of placebo-treated patients and higher rates of subsequent life-prolonging therapy for the placebo group.

Annals of Oncology

Apalutamide and Overall Survival in Non-Metastatic Castration-Resistant Prostate Cancer

Ann. Oncol 2019 Sep 27;[EPub Ahead of Print], EJ Small, F Saad, S Chowdhury, S Oudard, BA Hadaschik, JN Graff, D Olmos, PN Mainwaring, JY Lee, H Uemura, P De Porre, AA Smith, K Zhang, A Lopez-Gitlitz, MR Smith