Administration of Nivolumab in Metastatic Renal Cell Cancer Following Treatment With mTOR Inhibitors.

BACKGROUND/AIM: Immunotherapy with checkpoint inhibitors is currently considered a cornerstone of metastatic renal clear cell cancer (mRCC) therapy. Despite the general improvement in the survival of patients with mRCC, there are some clinical situations that have not been specifically evaluated in clinical trials, such as the use of everolimus before nivolumab. PATIENTS AND METHODS: We performed a retrospective analysis evaluating the efficacy of nivolumab in the real-world setting, including a subset of patients with previous mTOR inhibitor therapy. RESULTS: From a total of 56 patients, 25 were pre-treated with everolimus before receiving nivolumab. The overall progression-free survival (PFS), overall survival (OS), and objective response rate were 10.3, 21.3 months, and 34%, respectively. There were no statistically significant differences in patients who were or were not pre-treated with everolimus. CONCLUSION: mRCC patients should be treated with checkpoint inhibitors and prior use of mTOR inhibitors should not be a definitive exclusion criterium.

High c-Myb Expression Associates with Good Prognosis in Colorectal Carcinoma.

Colorectal cancer (CRC) represents a serious challenge for oncologists due to high incidence and large heterogeneity. Prognostic factors are needed to stratify patients according to risk of disease progression. In this study, we report that high expression of c-Myb protein, determined by immunohistochemistry (IHC), associates with better overall and disease-free survival (OS, DFS) in a cohort of 103 patients. Although MYB has been previously considered to act as oncogene in CRC, our further analysis of datasets deposited in PrognoScan and SurvExpress databases confirmed that high MYB expression largely associates with good prognosis in CRC. As therapies targeting c-Myb have been developed and tested in preclinical studies, we believe that further studies are needed for detailed understanding of c-Myb function in CRC, before the c-Myb-targeted therapy enters clinical trials.

An observational, multicentre study of cabazitaxel in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (CAPRISTANA).

OBJECTIVES: To obtain routine clinical practice data on cabazitaxel usage patterns for patients with metastatic castration-resistant prostate cancer (mCRPC) and to describe physician-assessed cabazitaxel effectiveness, health-related quality of life (HRQoL) and safety. PATIENTS AND METHODS: CAPRISTANA was an international, observational cohort study examining cabazitaxel use for the treatment of patients with mCRPC. Effectiveness was assessed by overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF) and disease control rate. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate questionnaire (FACT-P) and the three-level European Quality of Life questionnaire (EQ-5D-3L). Safety was assessed by adverse event (AE) reporting. RESULTS: A total of 189 patients were treated across 54 centres between April 2012 and June 2016. At baseline, 58.7% had ≥1 comorbidity, 93.7% had an Eastern Cooperative Oncology Group performance status ≤1, and 60.1% had a Gleason score at diagnosis of ≥8. Patients received a median of 6 cabazitaxel cycles; 84.7% received cabazitaxel as second-line therapy. The median OS, PFS and TTF were 13.2, 5.6 and 4.4 months, respectively. Cabazitaxel led to disease control in 52.9% of patients. HRQoL was maintained (40.3%) or improved (32.2%) in 72.5% of patients based on total FACT-P scores. Interestingly, 53.6% of patients reported pain improvement and a further 21.2% maintained pain control based on FACT-P prostate cancer-specific pain scores. The most common treatment-related grade ≥3 AEs were neutropenia (7.9%) and anaemia (2.1%). CONCLUSION: Patients in CAPRISTANA treated with cabazitaxel had similar disease outcomes and safety profiles compared with large phase III clinical trials. Most patients had maintained or improved HRQoL scores; >70% of patients had maintained or improved pain control.

Overexpression of c-Myb is associated with suppression of distant metastases in colorectal carcinoma.

The MYB gene codes for the c-Myb transcription factor maintaining proliferation of colon epithelial progenitors, thus controlling colon development and homeostasis. This gene is overexpressed in early phases of colorectal cancer (CRC) tumorigenesis. The aim of this study was to examine the expression of c-Myb in CRC tissue samples both at the messenger RNA (mRNA) and protein levels and to evaluate their associations with clinicopathological characteristics in a group of 108 CRC patients. Statistically significant negative association was found between the frequency of the c-Myb-positive tumor cells assessed by immunohistochemistry and the presence of distant metastases (p < 0.01) but not tumor differentiation, tumor stage, lymph node involvement, vascular invasion, tumor localization, age, and gender of the patients. Although the c-Myb protein level in the tumor tissue correlated with its mRNA level, no significant association between MYB mRNA and any clinicopathological characteristics was observed. We conclude that albeit overexpression of c-Myb is considered as an important factor contributing to early phases of CRC tumorigenesis, it may later have negative effect on tumor cell dissemination as observed recently in breast cancer as well. Further studies are required to explain the role of c-Myb during formation of CRC distant metastases.