J&J Reports 62% EFS Risk Reduction With ERLEADA Plus ADT

Johnson & Johnson (J&J) has reported results from a Phase 3 PROTEUS substudy showing that perioperative treatment with apalutamide (ERLEADA) plus androgen deprivation therapy (ADT) reduced the hazard of an event-free survival (EFS) event by 62% compared with radical prostatectomy alone in patients with high-risk localized or locally advanced prostate cancer. The findings were presented as late-breaking abstract LBA53 at the European Society for Medical Oncology (ESMO) Congress 2026 on October 24 in Madrid. The manuscript has been accepted for publication in European Urology.

Addressing recurrence risk after surgery

Radical prostatectomy is a treatment option with curative intent for high-risk localized and locally advanced prostate cancer. However, some patients experience biochemical recurrence, local or distant progression, or require additional treatment after surgery.

Apalutamide is an androgen receptor inhibitor that blocks androgen signalling. It is approved for non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-sensitive prostate cancer (mCSPC), but not for high-risk localized or locally advanced disease. The PROTEUS program is evaluating whether adding systemic treatment around surgery can improve outcomes in this population.

PROTEUS substudy design

The randomized, open-label substudy (NCT03767244) included 408 patients with newly diagnosed, non-metastatic, high-risk localized or locally advanced prostate cancer who were candidates for surgery and systemic therapy. Of these, 102 received apalutamide plus ADT and 306 underwent radical prostatectomy alone.

In the combination arm, patients received apalutamide 240 mg orally once daily with ADT for six 28-day cycles before surgery and another six cycles after surgery. Radical prostatectomy with pelvic lymph-node dissection was performed between treatment periods. Apalutamide was paused two weeks before surgery and resumed four weeks afterward. Patients in the comparator arm underwent the same surgery, followed by standard institutional practice or observation.

The primary endpoint was EFS, defined as time to biochemical failure, local or regional recurrence, distant metastasis or death. Secondary endpoints included prostate-specific antigen (PSA)-free survival and metastasis-free survival (MFS), while time to first subsequent therapy and overall survival were exploratory endpoints.

EFS improved with perioperative combination treatment

At a median follow-up of 37.8 months, the combination regimen was associated with a hazard ratio (HR) of 0.38 for EFS (95% confidence interval [CI], 0.26–0.55; p<0.0001), representing a 62% relative reduction in the hazard of an EFS event. Median EFS was not reached with apalutamide plus ADT, compared with 19.1 months with surgery alone.

The estimated three-year EFS rates were 63% and 41.4%, respectively, a difference of 21.6 percentage points.

MFS also favored combination treatment, with an HR of 0.49 (95% CI, 0.26–0.90; nominal p=0.0193), corresponding to a 51% lower hazard of distant metastasis or death. For the exploratory endpoint of time to first subsequent therapy, the HR was 0.29 (95% CI, 0.20–0.43; nominal p<0.0001). At three years, 64.6% of patients receiving apalutamide plus ADT remained free from subsequent therapy, compared with 32% in the surgery-alone arm.

Overall-survival data are not yet available, and follow-up is ongoing.

 Safety findings

Grade 3 or 4 treatment-emergent adverse events occurred in 31% of patients receiving apalutamide plus ADT and 22% of those undergoing surgery alone. No treatment-emergent adverse events led to death in either arm. Hot flushes and urinary incontinence were the most frequently reported adverse events associated with apalutamide treatment, at 64% and 63%, respectively.

The higher rate of severe adverse events indicates that the efficacy findings should be considered alongside treatment tolerability. Because urinary incontinence can also follow prostatectomy, the reported percentage alone does not establish how much was attributable to apalutamide, ADT or surgery.

Clinical interpretation

The EFS improvement suggests that perioperative apalutamide plus ADT may delay biochemical or clinical disease events compared with surgery alone in this high-risk population. The favorable MFS and time-to-subsequent-therapy findings provide additional support for further evaluation, although the latter endpoints were reported with nominal p-values.

The comparator is an important limitation. Because the substudy compared the combination regimen with surgery alone and did not include an ADT-only arm, it cannot establish apalutamide’s independent contribution to the observed benefit. Its results also should not be directly compared with the primary PROTEUS study’s treatment effect, which was assessed against placebo plus ADT.

EFS includes PSA-based biochemical failure, so the observed benefit does not by itself demonstrate a reduction in mortality. The open-label design, unequal group sizes, relatively limited follow-up for a disease with a long natural history, and immature overall-survival data further limit conclusions.

The findings support continued investigation of perioperative systemic treatment for high-risk prostate cancer, but do not establish an overall-survival advantage or a new approved treatment option. Apalutamide plus ADT remains unapproved for this setting, and its eventual clinical role will depend on the full evidence base, longer-term outcomes and regulatory assessment.

References

ERLEADA (apalutamide) treatment before and after surgery reduces risk of recurrence or death by 62% versus surgery alone in high-risk prostate cancer, Johnson & Johnson, 24 October 2026

A Study of Apalutamide in Participants with High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy (PROTEUS), ClinicalTrials.gov ID NCT03767244