TY - JOUR
T1 - Improved outcomes in elderly patients with metastatic castration-resistant prostate cancer treated with the androgen receptor inhibitor enzalutamide
T2 - Results from the phase III AFFIRM trial
AU - Sternberg, Cora N.
AU - de Bono, J. S.
AU - Chi, K. N.
AU - Fizazi, K.
AU - Mulders, P.
AU - Cerbone, L.
AU - Hirmand, M.
AU - Forer, D.
AU - Scher, H. I.
N1 - Funding Information:
This work was supported by Medivation, Inc. and Astellas. Enzalutamide is being codeveloped by Medivation, Inc. and Astellas. Both companies sponsored the AFFIRM trial.
Funding Information:
The authors had full access to the data and participated in reviewing and interpreting the data and paper. They would like to thank Peter Flanagan and Eolas Communications for assistance with writing and revising the draft manuscript, based on detailed discussion and feedback from all authors. Writing assistance was funded by Astellas and Medivation. Primary responsibility for opinions, conclusions, and interpretation of data lies with the authors. All authors read and approved the final version of this manuscript.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Background: The randomized, double-blind phase III AFFIRM trial demonstrated that enzalutamide, an oral androgen receptor inhibitor, significantly prolonged overall survival (OS) [median 18.4 versus 13.6 months (hazard ratio, HR) 0.63 (95% confidence interval, CI, 0.53-0.75); P < 0.001] compared with placebo in patients with metastatic castration-resistant prostate cancer who received prior docetaxel chemotherapy. Patients and methods: A post hoc analysis was carried out to assess the efficacy and safety of enzalutamide on outcomes in younger (<75 years) and elderly (≥75 years) patients in the AFFIRM population. Statistics are presented by age group (<75 years, ≥75 years) for efficacy outcomes of OS, radiographic progression-free survival (rPFS), time to prostatespecific antigen (PSA) progression, PSA response, and safety. Results: OS was significantly improved with enzalutamide over placebo in patients <75 years [median not yet reached versus 13.6 months; HR 0.63 (95% CI 0.52-0.78), P < 0.001] and in patients ≥75 years [median 18.2 versus 13.3 months; HR 0.61 (95% CI 0.43-0.86), P ≥ 0.004], respectively. rPFS was similarly improved in both the younger [HR 0.45 (95% CI 0.38-0.53), P < 0.001] and elderly patient cohorts [HR 0.27 (95% CI 0.20-0.37), P < 0.001] relative to placebo, as were time to PSA progression and PSA response. Adverse events (AEs) were similar between the two enzalutamide age groups, with the exception of an increase in patients ≥75 years in the rates of all grade peripheral edema (22.1% versus 12.5%), fatigue (39.7% versus 31.6%), and diarrhea (26.6% versus 19.6%). The overall grade ≥3 AE rates were low with no major difference in frequency or severity between age groups or treatment arms. Five patients were reported with seizure events; three patients <75 years and two patients ≥75 years. Conclusions: Enzalutamide significantly improves outcomes in both younger (<75 years) and elderly patients (≥75 years), with comparable safety and tolerability.
AB - Background: The randomized, double-blind phase III AFFIRM trial demonstrated that enzalutamide, an oral androgen receptor inhibitor, significantly prolonged overall survival (OS) [median 18.4 versus 13.6 months (hazard ratio, HR) 0.63 (95% confidence interval, CI, 0.53-0.75); P < 0.001] compared with placebo in patients with metastatic castration-resistant prostate cancer who received prior docetaxel chemotherapy. Patients and methods: A post hoc analysis was carried out to assess the efficacy and safety of enzalutamide on outcomes in younger (<75 years) and elderly (≥75 years) patients in the AFFIRM population. Statistics are presented by age group (<75 years, ≥75 years) for efficacy outcomes of OS, radiographic progression-free survival (rPFS), time to prostatespecific antigen (PSA) progression, PSA response, and safety. Results: OS was significantly improved with enzalutamide over placebo in patients <75 years [median not yet reached versus 13.6 months; HR 0.63 (95% CI 0.52-0.78), P < 0.001] and in patients ≥75 years [median 18.2 versus 13.3 months; HR 0.61 (95% CI 0.43-0.86), P ≥ 0.004], respectively. rPFS was similarly improved in both the younger [HR 0.45 (95% CI 0.38-0.53), P < 0.001] and elderly patient cohorts [HR 0.27 (95% CI 0.20-0.37), P < 0.001] relative to placebo, as were time to PSA progression and PSA response. Adverse events (AEs) were similar between the two enzalutamide age groups, with the exception of an increase in patients ≥75 years in the rates of all grade peripheral edema (22.1% versus 12.5%), fatigue (39.7% versus 31.6%), and diarrhea (26.6% versus 19.6%). The overall grade ≥3 AE rates were low with no major difference in frequency or severity between age groups or treatment arms. Five patients were reported with seizure events; three patients <75 years and two patients ≥75 years. Conclusions: Enzalutamide significantly improves outcomes in both younger (<75 years) and elderly patients (≥75 years), with comparable safety and tolerability.
KW - AFFIRM trial
KW - Elderly patients
KW - Enzalutamide
KW - Metastatic castration-resistant prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=84893349290&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdt571
DO - 10.1093/annonc/mdt571
M3 - Article
C2 - 24478320
AN - SCOPUS:84893349290
SN - 0923-7534
VL - 25
SP - 429
EP - 434
JO - Annals of Oncology
JF - Annals of Oncology
IS - 2
ER -