Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, was approved by the US Food and Drug Administration for the treatment of advanced non-small-cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. ARIES (Avastin Regimens: Investigation of Effectiveness and Safety), a prospective observational cohort study, evaluated outcomes in a large, community-based population of patients with first-line NSCLC.
Development of new therapies for previously treated small-cell lung cancer (SCLC) is a major unmet need. Here, we describe a randomized, phase II trial of weekly topotecan with or without ziv-aflibercept (VEGF-trap) in this clinical setting.
Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in approximately 20% of invasive breast cancer cases and is associated with a more aggressive disease course than HER2-negative breast cancer. HER2-targeted therapies have altered the natural history of HER2-positive breast cancer, a trend that will likely further improve with the recent approval of new agents. A prospective, observational cohort study was designed and initiated to provide real-world insights into current treatment patterns, long-term survival, and patients' experiences with initial and subsequent treatments for HER2-positive metastatic breast cancer (MBC).
Breast cancer is the most common type of cancer among women and the second leading cause of cancer death in the United States. Metastatic breast cancer is considered incurable, and treatment is aimed at palliating symptoms, achieving remission, and prolonging survival. Treatment options for metastatic disease vary based on tumor surface markers and clinical factors in an individual patient and include cytotoxic chemotherapy, hormonal therapy, biological therapy, or some combination of these. An important molecular determinant of therapy is the human epidermal growth factor receptor 2 (HER2) positivity of the tumor, which affects response to HER2-targeted treatment. HER2 is a member of the human epidermal growth factor receptor family of receptor tyrosine kinases, also known as the HER family, which activates signaling that promotes tumorigenic cellular processes such as proliferation and evasion of apoptosis. Several targeted agents, including monoclonal antibodies and tyrosine kinase inhibitors that inhibit one or more HER family receptors have been developed that affect signaling through this pathway. Some of these, such as trastuzumab and lapatinib, have been approved for breast cancer treatment. Resistance to therapy is a challenge that limits the duration of benefit achieved with these agents. Therefore, combinations of HER family-targeted agents with other therapies such as cytotoxic agents, hormonal therapy, or inhibitors of other cellular pathways, are being developed to exploit synergy and overcome resistance mechanisms. Here we review the HER family-targeted agents currently approved or in development for HER2-positive metastatic breast cancer with a focus on strategies to overcome tumor resistance.
Non-small-cell lung cancer (NSCLC) is frequently characterized by metastases to bone. Bisphosphonates have demonstrated efficacy in reducing the risk of skeletal-related events in cancer patients with bone metastases, including those with NSCLC. Zoledronic acid (ZA) is one of the most potent bisphosphonates and is approved for the first-line treatment of patients with multiple myeloma and bone metastases from solid tumors. Recent preclinical and clinical data suggest that ZA may also have direct and indirect anticancer effects. Several preclinical studies have provided insight into the potential mechanisms responsible for the anticancer activity of ZA, including inhibiting farnesyl pyrophosphate or geranylgeranyl pyrophosphate and activation of immune-mediated anticancer response by ?? T cells. In patients with NSCLC, ZA has been shown to reduce vascular endothelial growth factor levels with a direct correlation to clinical response. Clinical studies in this setting have shown that ZA may also provide a survival benefit and prolong time to progression. Ongoing studies are evaluating the efficacy of ZA for anticancer activity and prevention of bone metastases. Bisphosphonates, particularly ZA, are generally well tolerated and may likely offer an adjunct therapeutic option for patients with NSCLC.
REMS are a particularly important issue for oncology and the National Comprehensive Cancer Network (NCCN). A disproportionate number of drugs with complex REMS are used in patients with cancer or hematologic disorders. REMS policies and processes within oncology may act as a model for other clinical areas. A breadth of experience and access to a wide knowledge base exists within oncology that will ensure appropriate development and consideration of the practical implications of REMS. NCCN is uniquely positioned to assume a leadership role in this process given its status as the arbiter of high-quality cancer care based on its world-leading institutions and clinicians. Notwithstanding the potential benefits, the successful design, implementation, and analysis of the FDAs recent requirement for REMS for some high-risk drugs and biologics will present significant challenges for stakeholders, including patients, providers, cancer centers, manufacturers, payors, health information technology vendors, and regulatory agencies. To provide guidance to these stakeholders regarding REMS challenges, the NCCN assembled a work group comprised of thought leaders from NCCN Member Institutions and other outside experts. The Work Group identified challenges across the REMS spectrum, including the areas of standardization, development and assessment of REMS programs, medication guides, provider knowledge and impact on prescribing, provider burden and compensation, and incorporation of REMS into clinical practice.
Bisphosphonates (BPs) are approved for preventing the skeletal-related events associated with malignant bone disease. Several studies indicate that they may also prevent cancer therapy-induced bone loss. Multiple preclinical and early clinical studies provide evidence of the anticancer activity of BPs, including an inhibition of tumor cell proliferation and survival, a reduction of angiogenesis, and a stimulation of innate anticancer immunity. In addition to their evident single-agent activity, BPs may also act synergistically with other antineoplastic agents. Translational studies corroborate the effects of bisphosphonates on angiogenesis and innate immunity. Moreover, many of these anticancer effects occur at clinically relevant drug concentrations. Indeed, clinical data suggest that in addition to being well-tolerated and efficacious in maintaining bone health, BPs including clodronate, pamidronate, and zoledronic acid also improve cancer-related outcomes such as tumor response, disease-free survival, and overall survival in patients with breast cancer. Among the BPs, zoledronic acid is the most extensively studied in the adjuvant and neoadjuvant settings and has accumulated the most data pointing to anticancer activity, although a survival benefit has not been documented. Future studies are necessary to elucidate the anticancer activity of BPs. Other aspects of BP therapy that require further study include the optimization of dosing regimens for single agents and combinations in various clinical settings and the identification of prognostic factors that predict treatment outcomes. This review summarizes the preclinical and clinical evidence of anticancer activity of BPs, with a focus on zoledronic acid.
Published data from the Middle East and North Africa (MENA) region indicate suboptimal quality of cancer care, while the World Health Organization predicts an increase in cancer cases in developing countries. Major advances in breast cancer management mandate the development of guidelines to improve the quality and efficacy of oncology practice in the MENA region. A Breast Cancer Regional Guidelines Committee was organized and activated, comprising experts from various regional cancer institutions. The multidisciplinary team included 12 medical oncologists, 3 radiation oncologists, 2 radiologists, 2 surgeons, and 1 pathologist. The committee members agreed on adapting the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Breast Cancer for use in the MENA region to achieve common practice standards for treating patients. The members suggested several modifications to the guidelines, especially those related to risk factor profiles. United States-based NCCN experts reviewed these recommendations before final approval. The MENA-NCCN Breast Cancer Guidelines modification process was the first initiative in the development of common practice guidelines in the region. This project may serve as a foundation for the development of evidence-based practice standards, and improve collaborative projects and initiatives.
A lung cancer committee from the Middle East and North Africa (MENA) region was established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Non-Small Cell Lung Cancer to create a platform for standard care in the region. The committee comprised different experts in thoracic oncology from the region, including the disciplines of medical and clinical oncology, radiation oncology, thoracic surgery, pulmonary medicine, radiology, and pathology. The committee reviewed version 2 of the 2009 NCCN Guidelines on Non-Small Cell Lung Cancer and identified recommendations requiring modification for the region using published evidence and relevant experience. These suggested modifications were discussed among the group and with a United States-based NCCN expert for approval. The recommended modifications, with justification and references, were categorized based on the NCCN Guidelines flow. This article describes these recommended modifications. The process of adapting the first NCCN-based guidelines in the region is a step toward helping to improve lung cancer care in the region and encouraging networking and collaboration.
The NCCN developed clinical practice guidelines for oncology that set the standard of cancer care in the United States. Because of wide acceptance of, need for, and interest in standardized treatment practices across the world, NCCN launched initiatives to help international groups adapt these guidelines. This article describes the initiative in the Middle East and North Africa (MENA) region. A group of oncology experts and key opinion leaders were assembled into 7 specific committees to develop treatment guidelines for breast cancer, lung cancer, colon cancer, prostate cancer, hepatobiliary cancer, lymphoma, and palliative care. The committees reviewed the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to identify any modifications required for them to be more applicable to the MENA region based on available evidence and regional experience. These modifications were discussed with NCCN experts and summarized for each specific area. The development of these guidelines generated a strong interest in the region to develop more evidence-based practice and create further networking and collaboration.
Bone metastases are a common complication in patients with advanced lung cancer, and most patients with bone metastases from lung cancer develop skeletal-related events (SREs). Skeletal-related events adversely impact patient quality of life and clinical outcome and are associated with increased costs of clinical management, underscoring the need for SRE prevention. Because current practice guidelines do not recommend pretreatment bone scans for all patients at initial presentation, skeletal involvement is not detected in a proportion of patients with early stage asymptomatic bone metastases. In addition, there are no uniform guidelines outlining treatment for patients with bone metastases. Although many bisphosphonates have not been investigated in this setting, zoledronic acid has proven efficacy in delaying the onset and reducing the risk of SREs in patients with bone metastases from lung cancer. Further, recent exploratory analyses in patients with bone metastases from solid tumors suggest that, in addition to normalizing biochemical markers of bone metabolism, zoledronic acid may improve survival in specific patient subsets, including those with lung cancer. Accordingly, several prospectively designed clinical trials assessing anticancer activity of zoledronic acid in the adjuvant setting are ongoing. New insights into the clinical relevance of bone-conserving therapy in patients with lung cancer are discussed.
There is discordance among studies assessing the impact of race on outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC treated at an urban cancer center in Memphis, TN with a predominant AA patient population.
Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.
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