Safety and Efficacy of RAD001 (Everolimus) Administered Upon Relapse During or After Adjuvant Treatment in Post-menopausal Women With Hormone Receptor Positive, HER2/neu Negative Locally Advanced or Metastatic Breast Cancer (CRAD001JGR08 "MELPOMENI" study).

BACKGROUND/AIM: This study aimed to provide real-world safety and effectiveness data of everolimus (EVE) plus exemestane (EXE) in estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced breast cancer (aBC). PATIENTS AND METHODS: This prospective observational study was conducted by 19 hospital-based oncologists in Greece. Eligible patients were treated with EVE+EXE in the first-line setting; EVE was initiated according to the approved label. RESULTS: Overall, 75 eligible patients (mean age: 66.9 years; visceral metastases: 49.3%; bone-only metastases: 37.3%) were included in the effectiveness analyses. Over a median (interquartile range) of 12.1 months (range=4.2-20.5 months) of EVE treatment, the median progression-free survival was 18.0 months and the overall response rate was 22.7%. Among patients that received ≥1 EVE dose (n=80), the incidence of EVE-related adverse events was 72.5% (serious: 55.0%); stomatitis (22.5%), fatigue (22.5%), pneumonitis (18.8%); and cough (18.8%) were the most common. CONCLUSION: In the routine care in Greece, EVE demonstrates clinical benefit and a predictable safety profile.

Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer: The Triumph of Radiobiology.

BACKGROUND: Radiotherapy represents one of the main therapeutic modalities for localized prostate cancer. In the last two decades, emerging data regarding the radiobiology of prostate cancer suggests a very low α/ß value, which has led the scientific community to evaluate the potential advantage of hypofractionation. OBJECTIVE: The aim of this manuscript is to present the rationale of prostate radiobiology and the medical evidence of moderate hypofractionation for prostate cancer. METHODS: Existing literature was reviewed, including data from prospective clinical trials dealing with the efficacy and toxicity of hypofractionated radiotherapy. Fifteen prospective phase II studies, nine randomized phase III studies and ten meta-analyses were selected. For every study included, the equivalent dose was calculated for both biochemical control and late toxicity. RESULTS: The efficacy of hypofractionated radiotherapy, compared to conventional radiotherapy, regarding biochemical control, was evaluated in five superiority and four non-inferiority randomized phase III studies. The majority of participants in these studies were patients with low- and intermediate- risk prostate cancer. Even though the superiority criterion of the hypofractionation was not met in all studies, the noninferiority criterion was met. Prospective phase II studies of hypofractionation reported a low rate of acute and late toxicity. In randomized phase III studies, acute and late toxicity grade 3 and higher for the bowel and bladder was comparable between hypofractionated and conventional radiotherapy. The included meta-analyses showed no difference in efficacy and toxicity. CONCLUSION: Moderate hypofractionation is feasible and safe, and may be considered as an alternative option in low- and intermediate-risk prostate cancer patients.