Non-metastatic castration-resistant prostate cancer - ESMO Clinical Practice Guidelines
Castration-resistant prostate cancer ( CRPC ) is defined as disease progression during ADT ( androgen deprivation therapy ), with serum testosterone at castrate levels.
The absence of metastases ( M0 ) on traditional imaging ( bone scintigraphy and CT scan ) has been used to identify M0 CRPC disease.
This disease setting exists because of the use of early, long-term ADT for men with non-metastatic prostate cancer.
If ADT is delayed in men with biochemical failure after radical treatment until the site of recurrence is detected, M0 CRPC will be unusual because men will typically only develop castration-resistant disease after the detection of metastases.
Apalutamide significantly increased median metastasis-free survival ( 40.5 months versus 16.2 months, hazard ratio, HR 0.28; 95% CI 0.23-0.35 ) and time to symptomatic progression ( HR 0.45; 95% CI 0.32-0.63 ) as compared with placebo in amulticentre, randomised, placebo-controlled, phase III trial ( SPARTAN ) conducted in 1207 men with high-risk M0 CRPC( baseline PSAmore than 2.0 ng/ml and a PSA doubling time of less than or equal to 10months ).
Data on overall survival are still immature ( HR 0.70; 95% CI 0.47-1.04 ).
The most frequent side-effects observed in the experimental arm were rash, hypertension, fracture, hypothyroidism and mental-impairment disorder.
Enzalutamide was evaluated in patients with high-risk M0 CRPC ( PROSPER trial ). In 1401 patients, Enzalutamide was superior to placebo with regard to the primary end point of median metastasis-free survival ( 36.6 months versus 14.7months, HR 0.29; 95% CI 0.24-0.35 ), and the key secondary endpoints of median time to PSA progression ( 37.2 versus 3.9 months; HR 0.07; 95% CI 0.05-0.08 ) and time to subsequent antineoplastic therapy ( 39.6 versus 17.7 months; HR 0.21; 95% CI 0.17-0.26 ).
Data on overall survival are still immature.
Side-effects most commonly reported in the Enzalutamidegroup were fatigue, hypertension, adverse cardiovascular events and mental-impairment disorders.
Darolutamide was evaluated in the ARAMIS trial, a multicentre, randomised, double-blind, placebo-controlled, phase III trial involving 1509 men with high-risk M0 CRPC and a PSA doubling time of less than or equal to 10 months.
Darolutamide significantly increased the median metastasis-free survival compared with placebo ( median 40.4 months versus 18.4months; HR 0.41; 95% CI 0.34-0.50 ).
Data on overall survival are immature.
Grade 3 or 4 adverse events were reported in 19.5% versus 24.7% of patients receiving placebo and Darolutamide, respectively.
Apalutamide [ ESMO-MCBS v1.1 score: 3 ], Darolutamide [ ESMO-MCBS v1.1 score: 3 ] or Enzalutamide [ ESMO-MCBS v1.1 score: 3 ] should be considered as options for men with M0 ( on bone scan and CT ) CRPC and a high risk of disease progression [ I, B ]. ( Xagena )
Source: Prostate cancer: ESMO Clinical Practice Guidelines, 2020
Apalutamide vs placebo in patients with non-metastatic castration-resistant prostate cancer receiving androgen deprivation therapy: health-related quality of life at final analysis of the SPARTAN study
The phase III SPARTAN study evaluated Apalutamide ( Erleada ) vs Placebo in patients with non-metastatic castration-resistant prostate cancer (...
European Union: Lynparza approved for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer
Lynparza ( Olaparib ) has been approved in the European Union ( EU ) for patients with metastatic castration-resistant prostate...
European Commission has approved expanded use of Erleada for treatment of patients with metastatic hormone-sensitive prostate cancer
The European Commission ( EC ) has granted marketing authorisation for the expanded use of Erleada ( Apalutamide ) to...
Apalutamide versus placebo in patients with nonmetastatic castration-resistant prostate cancer: final survival results from SPARTAN, a phase III trial
SPARTAN has evaluated Apalutamide ( Erleada ) versus placebo in patients with nonmetastatic castration-resistant prostate cancer ( nmCRPC ) and...
Darolutamide added to androgen deprivation therapy for nonmetastatic castration-resistant prostate cancer: overall survival results of phase III ARAMIS study
Darolutamide ( Nubeqa ) is a structurally distinct androgen receptor inhibitor with a favorable safety profile, approved for treating men...
IPATential150 study: Ipatasertib in combination with Abiraterone and Prednisone / Prednisolone met its co-primary endpoint of radiographic progression free survival in patients with PTEN loss tumours
Tthe phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival ( rPFS ) in patients with metastatic...
Erleada for non-metastatic castration-resistant prostate cancer patients who are at high risk of developing metastatic disease, European Commission approved
The European Commission ( EC ) has granted marketing authorisation for Erleada ( Apalutamide ), a next generation oral androgen...
Apalutamide improves overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer
Results from the phase 3 TITAN study were presented in an oral session at the American Society of Clinical...
For patients with prostate cancer, treating the disease with androgen deprivation therapy ( ADT ) is linked to a...