Efficacy, patient-reported outcomes (PROs), and tolerability of the changing therapeutic landscape in patients with metastatic prostate cancer (MPC): a systematic literature review.
OBJECTIVE
New therapies have attempted to improve on efficacy outcomes observed with docetaxel in patients with metastatic prostate cancer (MPC) who are hormone-therapy refractory or castration-resistant. In addition to the efficacy, patient-reported outcomes (PROs) and tolerability need to be assessed to define treatment benefit, as PROs measure the patient's subjective experience and can be correlated with hard outcomes. The main objective of this study was to evaluate the survival benefit of new therapies and secondary efficacy-related outcomes. Assessment of the number of studies reporting PROs and tolerability was also conducted.


METHODS
A predefined search strategy was conducted on major academic/governmental databases and conference proceedings (2007-2011). Exclusion criteria were applied.


RESULTS
Of 77 studies identified, 26 (34%) evaluated survival as an end point; 14 (18%) assessed PROs/tolerability. In chemotherapy-naive patients (no/minimal symptoms), median overall survival (OS) was 26 months for sipuleucel-T. In relapsed patients, the survival benefit of cabazitaxel/abiraterone was 15 months and that of enzalutamide was 18 months. Denosumab prolonged time to first on-study skeletal-related event (20.7 months denosumab, 17.1 months zoledronic acid; P = 0.0002, noninferiority; P = 0.008, superiority). Similar benefit was documented with radium-223, a new bone-targeted α-particle-emitting radiopharmaceutical. Radium-223 also significantly improved the OS (two-sided P = 0.00185). Specific to PROs, they were incorporated primarily as secondary end points, and improvements in pain response (most commonly evaluated) were variable among the agents. Last, the therapies were associated with unique toxicities requiring careful consideration.


CONCLUSIONS
The results of this review demonstrate that the therapeutic landscape of MPC has changed dramatically and many therapies in MPC now show OS improvements of about 4 months in the postdocetaxel setting.
Bayer HealthCare Pharmaceuticals, Inc., Wayne, NJ 07470, USA. brian.seal@bayer.com
Brian S
BS
Seal
Carl V
CV
Asche
Katarzyna
K
Puto
Pamela D
PD
Allen
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D019496:Cancer Vaccines / Q000627:therapeutic use; D018450:Disease Progression; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology*; D011868:Radioisotopes / Q000627:therapeutic use; D016019:Survival Analysis; D014020:Tissue Extracts / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D005938:Glucocorticoids; D011868:Radioisotopes; D014020:Tissue Extracts; C511774:sipuleucel-T; D017430:Prostate-Specific Antigen
bone metastases; castration-resistant prostate cancer; chemotherapy; hormonal therapy; overall survival; patient-reported outcomes; prostate cancer; radiopharmaceuticals; skeletal-related events