New data show Johnson & Johnson’s Erleada (apalutamide) and Xtandi (enzalutamide) from Pfizer Inc. and Astellas Pharma Inc. both prolonged overall survival in men with non-metastatic castration-resistant prostate cancer (nmCRPC).

J&J’s Erleada, combined with androgen deprivation therapy (ADT), prolonged median overall survival by 14 months and reduced the risk of death by 22% compared to ADT alone. The data come from the final analysis of the company’s phase III SPARTAN study of patients with nmCRPC who were at high risk of developing metastases. The median overall survival rate was 73.9 months for patients receiving treatment with apalutamide in combination with ADT compared to 59.9 months with patients receiving placebo in combination with ADT. To reach statistical significance, a “p” value of p<0.046 needed to be observed; the final value was p=0.0161.

The SPARTAN study, a randomized, registrational, double-blind, placebo-controlled, multicenter study, also met all its secondary and exploratory endpoints. The secondary endpoints were time to metastasis, progression-free survival (PFS), time to symptomatic progression, overall survival and time to initiation of cytotoxic chemotherapy. The exploratory endpoints were second progression-free survival (PFS2), PSA responses and risk of PSA progression.

SPARTAN enrolled 1,207 patients who were randomized 2-to-1 to receive either apalutamide orally at a dose of 240 mg once daily in combination with ADT or placebo once daily in combination with ADT.

Erleada is an androgen receptor inhibitor indicated for use in Europe to treat adult men with nmCRPC who are at high risk of developing metastatic disease and in adult men for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with ADT. In the U.S., apalutamide is indicated for the treatment of nmCRPC and mHSPC.

PROSPER meets endpoint

The Xtandi data, from the phase III PROSPER trial from Pfizer and Astellas, resulted in a statistically significant 27% reduced risk of death compared with placebo, demonstrating that initiation of Xtandi and ADT before the onset of detectable metastasis improves overall survival in men with castration-resistant prostate cancer and rapidly rising PSA, the company said.

The new data were from the PROSPER study’s final overall survival analysis. Astellas and Pfizer hinted at the overall survival numbers in February but did not reveal them at the time, saying only that the results, a key secondary endpoint, marked a statistically significant improvement. The study met its primary endpoint of metastasis-free survival (p<0.001) in men with nmCRPC and rapidly rising PSA who received Xtandi.

The phase III PROSPER study, a randomized, double-blind, placebo-controlled, multinational trial, enrolled about 1,400 patients in the U.S. Canada, Europe, South America and the Asia-Pacific region. Patients had no symptoms and no prior or present evidence of metastatic disease. The trial evaluated enzalutamide at a dose of 160 mg taken orally once daily plus ADT, vs. placebo plus ADT. The primary endpoint was the time from patients entering the trial until their cancer was radiographically detected as having metastasized, or until death, within 112 days of treatment discontinuation. Key secondary endpoints included overall survival, time to PSA progression and time to first use of antineoplastic therapy.

The indication nmCRPC refers to a disease stage in which the cancer no longer responds to treatments that lower testosterone but has not been found in other parts of the body using a total body bone scan and/or CT/MRI scan.

Both sets of findings are previews of presentations to be made at the upcoming and virtual American Society of Clinical Oncology conference, which begins May 29.

No Comments