Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO Study Group metadatabase.

OBJECTIVE: Since almost two decades standard 1st-line chemotherapy for advanced ovarian cancer (AOC) has been a platinum/taxane combination. More recently, this general strategy has been challenged because different types of AOC may not benefit homogenously. Low-grade serous ovarian cancer (LGSOC) is one of the candidates in whom efficacy of standard chemotherapy should be revised. METHODS: This study is an exploratory case control study of the AGO-metadatabase of 4 randomized phase III trials with first-line platinum combination chemotherapy without any targeted therapy. Patients with advanced FIGO IIIBIV low-grade serous ovarian cancer were included and compared with control cases having high-grade serous AOC. RESULTS: Out of 5114 patients in this AGO database 145 (2.8%) had LGSOC and of those thirty-nine (24.1%) had suboptimal debulking with post-operative residual tumor >1cm, thus being eligible for response evaluation. An objective response was observed in only 10 patients and this 23.1% response rate (RR) was significantly lower compared to 90.1% RR in the control cohort of high-grade serous ovarian cancer (HGSOC) (p<0.001). Both, LGSOC and HGSOC patients who underwent complete cytoreduction had significantly better progression free survival (PFS) and overall survival (OS) in comparison to those with residuals after primary surgery, accordingly (p<0.001). CONCLUSIONS: Our observation indicates that low-grade serous cancer is not as responsive to platinum-taxane-based chemotherapy as high-grade serous AOC. In contrast, surgical debulking showed a similar impact on outcome in both types of AOC thus indicating different roles for both standard treatment modalities. Systemic treatment of low grade serous AOC urgently warrants further investigations.

Differences in the receptor status between primary and recurrent breast cancer--the frequency of and the reasons for discordance.

OBJECTIVE: Receptor discordances between primary and recurrent breast cancer have been described for years, but only a few analyses have elucidated the factors that influence receptor changes. METHODS: Explorative analyses of prospective data from a breast cancer database of a tertiary breast cancer unit. RESULTS: Recurrent tumours that had expressed oestrogen (ER) and progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) as primary tumours were negative for the respective receptor in 22.8, 41.4 and 40.8% of cases. ER, PR and HER2 expression was found in 19.8, 16.7 and 11.5% of recurrent tumours, although no expression had been observed in primary tumours. Receptor discordances in recurrent disease leading to different therapeutic approaches were noted in 126 of 411 patients (30.7%). In patients with tumours expressing primary ER and HER2, independent factors associated with discordance were endocrine therapy and treatment with trastuzumab. CONCLUSION: High rates of receptor discordance were found. The impact of factors that influence receptor changes is small so that no subgroup of patients with recurrent breast cancer should be excluded from biopsy. Whenever possible, a biopsy should be taken to confirm the diagnosis of a possible relapse as well as the receptor status of patients with breast cancer.

Bevacizumab in the treatment of ovarian cancer.

INTRODUCTION: In the past decade there have been many attempts to improve systemic treatment and thus the outcome of patients with ovarian cancer. However, neither the sequential addition of non cross-resistant drugs to standard chemotherapy comprising carboplatin and paclitaxel, nor triplet combination therapies with conventional chemotherapeutic drugs have improved outcomes. Instead, such approaches have led to an increase in the incidence of side effects. We are currently experiencing a shift toward the addition of molecularly targeted and biological anticancer therapies to standard treatment. Vascular endothelial growth factor (VEGF), which improves vitally important tumor vasculature, is secreted by a range of tumors, and a high level of VEGF is known to be an independent risk factor for aggressive disease in ovarian cancer. This finding led to the development in the 1990s of bevacizumab, a humanized monoclonal antibody against VEGF. DISCUSSION: Several phase II trials and four phase III trials have demonstrated that bevacizumab is active in patients with advanced and recurrent ovarian cancer. Both phase III trials of bevacizumab as first-line therapy in advanced ovarian cancer (ICON 7/AGOOVAR 11 and GOG-0218) have shown that the addition of bevacizumab to chemotherapy and as maintenance therapy improves progressionfree survival (PFS). The phase III trials in platinum-sensitive (OCEANS) and platinumresistant, relapsed disease (AURELIA) have also demonstrated a benefit for bevazicumab with respect to PFS. The administration of bevacizumab to improve survival in patients with ovarian cancer is not without side effects and a broad discussion on the cost-effectiveness of this approach is ongoing. CONCLUSION: This article presents clinical trial data on bevacizumab in the treatment of ovarian cancer and discusses the indication and pitfalls in the application of bevacizumab in patients with this malignancy.