Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial.

BACKGROUND: Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC. OBJECTIVE: To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC. DESIGN, SETTING, AND PARTICIPANTS: Retrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For the first three lines of salvage treatment for mCRPC we investigated the biochemical progression-free survival, maximum prostate-specific antigen (PSA) decline, overall survival, and tolerance. RESULTS AND LIMITATIONS: Overall, 245 patients received at least one treatment for mCRPC. For docetaxel used in first-line, a PSA decline ≥50% was observed in 25/66 (38%) and in 4/20 patients (20%) who had received upfront ADT alone and ADT plus docetaxel (p=0.14). The median biochemical progression-free survival was 6.0 mo (95% confidence interval: 3.6-7.7) and 4.1 mo (95% confidence interval: 1.3-4.9), respectively. For docetaxel used in first- or second-line, a PSA decline ≥50% was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront ADT alone and ADT plus docetaxel (p=0.07). PSA declines ≥50% were observed with bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved a PSA decline ≥50%. Few grade 3-4 events occurred. Study limitations include the observational design and retrospective characteristics of this analysis, without standardized therapeutic salvage protocols, and the limited number of patients in some of the treatment subgroups. CONCLUSIONS: Docetaxel rechallenge following progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only in a limited number of patients. Available data on abiraterone and enzalutamide support maintained efficacy in this setting. The lack of standardized therapeutic protocols for men developing mCRPC limits the comparability between patients. PATIENT SUMMARY: Rechallenging docetaxel at castration-resistance was active only in a limited number of patients treated upfront with chemo-hormonal therapy for metastatic castration-naive prostate cancer. Anticancer activity was suggested with abiraterone or enzalutamide in this setting.

[Home-based zoledronic acid infusion therapy in patients with solid tumours: compliance and patient-nurse satisfaction]. / Traitement à domicile par l'acide zolédronique chez des patients atteints de tumeurs solides : observance et satisfaction du patient et de l'infirmier.

PURPOSE: To explore patient and nurse satisfaction, compliance with best practice, technical feasibility and safety of home infusion of a bisphosphonate. METHODS: Prospective 1-year survey of home zoledronic acid therapy (4 mg, 15-min intravenous, every three to four weeks) in patients with bone metastases secondary to a solid malignancy. A physician questionnaire, nurse satisfaction/feasibility questionnaire and patient satisfaction questionnaire were administered. RESULTS: Physician participation rate: 56.5% (87/154); 818 patients included; 381 predominantly community nurses; 763/788 case report forms meeting inclusion criteria. PATIENT CHARACTERISTICS: median age, 68 years (30-95); M/F, 40/60; ECOG-PS 0 or 1, 78.6%; primary tumour site: breast (55.2%), prostate (28.4%), lung (7.2%), other (9.4%). Nurse satisfaction rates: 90.9% (organization of home ZOL therapy); 96.7% (ease of infusion); 97.5% (patient-nurse relationship); 73% (relationship with hospital staff). Patient satisfaction rates: 95.3% overall; 57.6% (quality of the nurse-patient relationship); 68.8% (less travel/waiting); 52.9% (consideration for home environment). Treatment tolerance: 33.63% (discontinuation due to adverse events); 0.6% (osteonecrosis of the jaw); 0.2% fractures. Practitioner compliance with best practice: 76.7% to 83.7% (recommended and/or tolerated dosage), 73% (dental hygiene checks at inclusion; 48 to 56% thereafter); 66% (pre-infusion hydration); often undocumented for calcium/vitamin D supplementation. CONCLUSION: Home zoledronic acid treatment was well tolerated. There was a very high level of both patient and nurse satisfaction with home therapy. However, better compliance with best practice should be encouraged.