Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis.
OBJECTIVE
Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA) and Western Europe. Androgen-deprivation therapy alone (ADT) remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT) that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel) for metastatic hormone-naive prostate cancer (mHNPC).


METHODS
Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (95% CI).


RESULTS
The final analysis included 3 trials comprising 2,264 patients (mHNPC). Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001), and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%). The biochemical progression-free survival (bPFS) also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001), also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%). Finally, the combination of ADT with docetaxel showed a superior overall survival (OS) compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001), with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%). A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002). In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003). Regarding adverse events and severe toxicity (grade ≥3), the group receiving the combined therapy had higher rates of neutropenia, febrile neutropenia and fatigue.


CONCLUSIONS
The combination of ADT with docetaxel improved the clinical progression-free survival, bPFS and OS of patients with mHNPC. A superior OS was seen especially for patients with metastatic and high-volume disease. This contemporary combination therapy may now be offered as a first-line treatment for selected patients.
Evidencias - A Kantar Health Company, Campinas, São Paulo, Brazil.|Comitê Brasileiro de Estudos em Uro-Oncologia - CoBEU, São Paulo, São Paulo, Brazil.
Tobias Engel Ayer
TE
Botrel
Evidencias - A Kantar Health Company, Campinas, São Paulo, Brazil.|Comitê Brasileiro de Estudos em Uro-Oncologia - CoBEU, São Paulo, São Paulo, Brazil.
Otávio
O
Clark
Comitê Brasileiro de Estudos em Uro-Oncologia - CoBEU, São Paulo, São Paulo, Brazil.
Antônio Carlos
AC
Lima Pompeo
Comitê Brasileiro de Estudos em Uro-Oncologia - CoBEU, São Paulo, São Paulo, Brazil.
Francisco Flávio
FF
Horta Bretas
Comitê Brasileiro de Estudos em Uro-Oncologia - CoBEU, São Paulo, São Paulo, Brazil.
Marcus Vinicius
MV
Sadi
Comitê Brasileiro de Estudos em Uro-Oncologia - CoBEU, São Paulo, São Paulo, Brazil.
Ubirajara
U
Ferreira
Comitê Brasileiro de Estudos em Uro-Oncologia - CoBEU, São Paulo, São Paulo, Brazil.
Rodolfo
R
Borges Dos Reis
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000627:therapeutic use*
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D043823:Taxoids; D050257:Tubulin Modulators; D000077143:Docetaxel