Real-world experience of abiraterone acetate plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: long-term results of the prospective ABItude study.

BACKGROUND: Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months. PATIENTS AND METHODS: We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated. RESULTS: Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved ≥50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR. CONCLUSION: With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: long term results of the Italian Tamoxifen Anastrozole trial.

The Italian Tamoxifen Anastrozole (ITA) trial investigated the efficacy of switching to anastrozole for women who were already on adjuvant tamoxifen since 2-3years. Relapse-free survival (RFS) was the primary end-point; event-free survival (EFS), overall survival (OS) and safety were secondary end-points. Herein, we report an update on the long term results of this trial. At a median follow-up time of 128 months (range 14-168 months), 94 events have been recorded in the tamoxifen group compared with 71 events in the anastrozole group (hazard ratio (HR)=0.71; 95% confidence interval (CI), 0.52-0.97; p=0.03). RFS was also significantly longer in the anastrozole group (HR=0.64; 95% CI, 0.44-0.94; p=0.023); no statistically significant difference between study arms concerning OS was shown, but the trial was not powered enough in respect to this end-point. The incidence of serious adverse events (SAE) like bone fractures was comparable (four in each arm), while gynaecological problems were still significantly more numerous among the women continued on tamoxifen (21 patients developed a SAE in this group, including eight endometrial cancers, compared to three patients who suffered from a SAE, including one endometrial cancer, in the anastrozole group: p<0.000). Present data confirm that switch is safe and can provide long-term gain in terms both of RFS and of EFS, which persists even several years since treatment discontinuation.

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian tamoxifen anastrozole (ITA) trial.

BACKGROUND: Tamoxifen, for many years the 'gold standard' in the adjuvant setting for the management of endocrine sensitive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy due to the development of resistance. This provided the rationale for a switching trial with anastrozole, the updated results of which are reported here. PATIENTS AND METHODS: This trial investigated the efficacy of switching to anastrozole for women already receiving tamoxifen. After 2-3 years of tamoxifen treatment, postmenopausal, node-positive, ER-positive patients were randomized to receive either anastrozole 1 mg/day or to continue tamoxifen, 20 mg/day, giving a total duration of 5-years treatment. The primary end point was disease-free survival and secondary endpoints were event-free survival, overall survival and safety. RESULTS: A total of 448 patients were enrolled. At a median follow-up time of 64 months (range 12-93), 63 events had been reported in the tamoxifen group compared with 39 in the anastrozole group [HR 0.57 (95% CI 0.38-0.85) P = 0.005]. Relapse-free and overall survival were also longer in the anastrozole group [HR 0.56 (95% CI 0.35-0.89) P = 0.01 and 0.56 (95% CI 0.28-1.15) P = 0.1]. However, the latter difference was not statistically significant. Overall more patients in the anastrozole group experienced at least one adverse event (209 versus 151: P = 0.000). However, numbers of patients experiencing serious adverse events were comparable (37 versus 40, respectively: P = 0.7). CONCLUSIONS: Switching to anastrozole after the first 2-3 years of treatment was confirmed to improve event-free and relapse-free survival of postmenopausal, node-positive, ER-positive early breast cancer patients already receiving adjuvant tamoxifen.

Serum enterolactone levels and the risk of breast cancer in women with palpable cysts.

Low levels of lignans, namely enterolactone, have been reported to be associated with an increased risk of breast cancer in the general female population. We assessed, retrospectively, the relationship between serum enterolactone concentrations and the occurrence of breast cancer in women with palpable cysts. The levels of enterolactone in cryopreserved serum aliquots, obtained from 383 women with palpable cysts at the time of their first cyst aspiration, were measured using a time-resolved fluoroimmunoassay (TR-FIA). After a median follow-up time of 6.5 years (range 0.5-12.75 years), 18 women were found to have developed an invasive breast cancer. Median values of serum enterolactone were significantly lower in women who subsequently developed breast cancer: 8.5 nM/l versus 16.0 nM/l: P=0.04. Odd Ratios (OR) for breast cancer were: 0.36 (P=0.03), 0.57 (P=0.3) and 0.38 (P=0.25) for 25th (8 nM/l), 50th (16 nM/l) and 75th (24 nM/l) percentile values, respectively. The receiver operating characteristic (ROC) analysis showed a satisfactory accuracy for enterolactone as a breast cancer risk indicator (area under the curve (AUC)=0.64: P=0.04). Logistic regression analysis confirmed that the enterolactone concentration had a strong protective effect on the breast cancer risk. These findings may have important clinical implications with regard to interventional diet-focused chemo-preventive trials.

Ifosfamide in urologic cancer.

The therapeutic activity of ifosfamide in urologic tumors has been reviewed. Ifosfamide has definite activity in nephroblastoma, where it represents the treatment of choice for children who are not cured by front-line chemotherapy, and for the adults who are diagnosed with this uncommon disease. Definite therapeutic activity has also been shown in patients with urothelial tract malignancies and it represents a major option for patients failing first-line cisplatin-based chemotherapy. However, promising results have been achieved in chemo-naïve patients in combination with taxanes or gemcitabine, though at the price of relevant toxicity. A modest activity has been shown by ifosfamide in renal cancer (including the sarcomatoid variant) and in hormone-refractory prostate cancer, which unfortunately respond poorly to cytotoxic chemotherapy. No results of ifosfamide in penile carcinoma are available so far.