The role of antiangiogenic agents in the treatment of patients with advanced colorectal cancer according to K-RAS status.

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide. Recently, it has been found that about 40 % of patients with CRC have mutations in the K-RAS gene. Several clinical trials have showed that patients with metastatic colorectal cancer (mCRC) who present tumour-promoting mutations in signalling pathways involving the epidermal growth factor receptor (EGFR), which includes activating K-RAS mutations, do not respond to anti-EGFR drugs such as panitumumab and cetuximab. Hence, K-RAS status is now considered an important negative predictive factor for response to anti-EGFR drugs. Moreover, K-RAS status seems to have also a prognostic role in CRC, but this fact is somewhat controversial. Activity of antiangiogenic agents seems not to be influenced by K-RAS gene status. Tumour angiogenesis has attracted interest in attempts to improve the management of mCRC. The vascular endothelial growth factor (VEGF) pathway is fundamental to the regulation of angiogenesis, and research has focused on developing agents that selectively target it. In this way, the anti-VEGF antibody bevacizumab in combination with chemotherapy has provided important clinical benefits in terms of response rate, progression-free survival and overall survival to patients with mCRC. Efficacy data of bevacizumab in K-RAS wild-type patients seem to be comparable with the efficacy data observed with anti-EGFR therapies in a cross-trial comparison. Although there is a lack of prospective and randomized data in this setting, the combination of chemotherapy plus antiangiogenic agents could be considered as an effective alternative for the treatment of mCRC with independence of K-RAS gene status. Here, we review the available data we have in the literature of the use of antiangiogenic strategies in the treatment of mCRC nowadays.

Long-term Clinical Outcomes of a Spanish Cohort of Metastatic Renal Cell Carcinoma Patients with a Complete Response to Sunitinib.

INTRODUCTION: The long-term clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) and a complete response (CR) to the tyrosine kinase inhibitor (TKI) sunitinib are poorly known. The characteristics of these patients could reveal previously undetected associations with clinical variables. PATIENTS AND METHODS: This observational, retrospective study (ATILA) used data from a registry of patients with mRCC who had received first-line sunitinib and had achieved CR from 2007 to 2018 in Spain. RESULTS: Sixty-two patients with CR were included; 48 patients (77.4%) received sunitinib in monotherapy and 14 (22.6%) combined with or followed by local treatment. Median age was 58.5 years (range, 32-81). Most patients (79.0%) had clear cell histology and had undergone previous nephrectomy (90.3%). The majority (70.2%) had an intermediate IMDC prognosis, 23% favorable and 7.0% poor. The median time on treatment with sunitinib was 28.2 months (IQR, 16.7-41.0) and the median time to CR was 10.9 months (IQR, 7.2-19.3). After a median follow-up of 8 years (range, 3-13 years), the median PFS was not reached. The overall median duration of complete response was 64.1 months (IQR, 32.2-99.4). The tolerance and safety profile of sunitinib was consistent with previous reports. CONCLUSION: Durable CR to sunitinib was observed in patients regardless the prognosis group, metastasis site or histology type, with 75% of patients remaining in CR after 10 years. CLINICALTRIALS: gov: NCT03916458.

Infective endocarditis in patients with oncological diseases. / Endocarditis infecciosa en pacientes con enfermedades oncológicas.

INTRODUCTION: Cancer patients may constitute a special risk group for the development of infective endocarditis (IE) because they are often subjected to invasive procedures. The aim of this study is to determine the differential clinical profile and prognosis of patients with IE and cancer. METHODS: A retrospective observational study was conducted on all patients consecutively diagnosed with IE in a single centre between 2005 and 2015. A comparative analysis was performed between patients with cancer and those free of disease, as well as a long-term follow-up. RESULTS: There were 208 IE cases, of which 32 had a cancer diagnosis. There were no significant differences in age (67.5 [59.2-74] vs. 64 [51-74] years). The Charlson comorbidity index was same whether cancer was diagnosed or not (4 [2.2-5] vs. 3.9 [2-5]). IE in cancer patients was mainly associated with health care (59.5% vs 24.4%, P<.001). Staphylococcus aureus was the main causative agent (35%), and the tricuspid location was three times more common (18.8% vs. 6.2%). Surgery was not performed in 18.7% of patients, despite having an indication, compared with 7.4% of patients without cancer. In-hospital mortality for cancer patients was 45.5%, and the probability of survival at one year was 40%. CONCLUSIONS: IE in patients with cancer is predominantly caused by staphylococci, and has high early mortality. Although it is often related to health care, patients are limited from the therapeutic point of view.

Prognostic and predictive biomarkers for somatostatin analogs, peptide receptor radionuclide therapy and serotonin pathway targets in neuroendocrine tumours.

Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms regarding their molecular biology, clinical behaviour, prognosis and response to therapy. Several attempts to establish robust predictive biomarkers have failed. Neither tissue markers nor blood borne ones have proven to be successful yet. Circulating tumour cells (CTCs) as "liquid biopsies" could provide prognostic information at the time a therapeutic decision needs to be made and could be an attractive tool for tumour monitoring throughout the treatment period. However, "liquid biopsies" are far from becoming the standard biomarker in NETs. Promising results have been presented over the last few years using a novel biomarker candidate, a multianalyte algorithm analysis PCR-based test (NETest). New technologies will open the field to different ways of approaching the biomarker conundrum in NETs. However, the complications derived from being a heterogeneous group of malignancies will remain with us forever. In summary, there is an unmet need to incorporate new biomarker candidates into clinical research trials to obtain a robust prospective validation under the most demanding scenario.

The Long-HER study: clinical and molecular analysis of patients with HER2+ advanced breast cancer who become long-term survivors with trastuzumab-based therapy.

BACKGROUND: Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression after trastuzumab treatment. METHODS: Data were collected from women with HER2-positive metastatic breast cancer treated with trastuzumab that experienced a response or stable disease during at least 3 years. Patients having a progression in the first year of therapy with trastuzumab were used as a control. Genes related with trastuzumab resistance were identified and investigated for network and gene functional interrelation. Models predicting poor response to trastuzumab were constructed and evaluated. Finally, a mutational status analysis of selected genes was performed in HER2 positive breast cancer samples. RESULTS: 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median duration of response was 55 months. The molecular analysis included 35 patients from the group with complete response and 18 patients in a control poor-response group. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival. Gene ontology analysis demonstrated that PI3K pathway was associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. CONCLUSIONS: Trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression after trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy.

Zoledronic acid in lung cancer with bone metastases: a review.

Lung cancer remains the leading cause of cancer mortality worldwide and bone metastases develop in approximately 30-40% of cases. Bisphosphonates are a key therapy for bone metastases; zoledronic acid is the only bisphosphonate with efficacy in preventing, reducing the incidence and delaying the onset of skeletal-related events controlling bone pain. Several bone metabolism markers indicate bone resorption activity, linking with prognosis and efficacy of zoledronic acid. Zoledronic acid has a well-established tolerability profile and can be administered safely as long-term therapy, although preventive measures are needed to avoid some severe side effects (nephrotoxicity and osteonecrosis of the jaw) found in a small number of patients receiving long-term therapy. Currently, lung cancer patients with bone metastases are candidates to receive zoledronic acid in clinical practice with demonstrated benefits and safety preserving quality of life. Additional roles in anticancer activity deserve attention and are under investigation.