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241 result(s) for "Lopes, Gilberto"
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Barriers in access to oncology drugs — a global crisis
In the past decade, oncologists worldwide have seen unprecedented advances in drug development and approvals but have also become increasingly cognizant of the rising costs of and increasing inequities in access to these therapies. These trends have resulted in the current problematic situation in which dramatic disparities in outcomes exist among patients with cancer worldwide owing, in part, to the lack of access to drugs that provide clinically meaningful benefits. In this Viewpoint, we have asked six oncologists working in different countries to describe how they perceive this issue in their region and propose potential solutions.
Management of colon cancer: resource-stratified guidelines from the Asian Oncology Summit 2012
Colon cancer is seen with increasing frequency in the Asia-Pacific region, and it is one of the most important causes of cancer mortality worldwide. This article reviews the available evidence for optimum management of colon cancer—in particular, with respect to screening and early detection of colon cancer, laparoscopic surgical treatment, adjuvant treatment of individuals with high-risk stage II and stage III cancer, palliative treatment of patients with metastatic disease, and management of resectable and potentially resectable metastases—and how these strategies can be applied in Asian countries with different levels of health-care resources and economic development, stratified by basic, limited, enhanced, and maximum resource levels.
Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-analysis
Abstract Context Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the Liraglutide Clinical Development Program, subjects treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA) had a higher absolute number of breast cancer events. Objective To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. Data Sources We searched MEDLINE, Embase, Web of Science, and CENTRAL from July 31, 2019 to February 8, 2020. Study Selection Reviewers assessed abstracts and full-text articles for RCTs of GLP-1RAs in adults with excessive weight and/or diabetes and a minimum follow-up of 24 weeks. Data Extraction Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Data Synthesis We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48 267 subjects treated with GLP-1RAs, 130 developed breast cancer compared with 107 of 40 755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76–1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48–2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. Conclusions Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms.
Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study
Oncogenic alterations in RET have been identified in multiple tumour types, including 1–2% of non-small-cell lung cancers (NSCLCs). We aimed to assess the safety, tolerability, and antitumour activity of pralsetinib, a highly potent, oral, selective RET inhibitor, in patients with RET fusion-positive NSCLC. ARROW is a multi-cohort, open-label, phase 1/2 study done at 71 sites (community and academic cancer centres) in 13 countries (Belgium, China, France, Germany, Hong Kong, Italy, Netherlands, Singapore, South Korea, Spain, Taiwan, the UK, and the USA). Patients aged 18 years or older with locally advanced or metastatic solid tumours, including RET fusion-positive NSCLC, and an Eastern Cooperative Oncology Group performance status of 0–2 (later limited to 0–1 in a protocol amendment) were enrolled. In phase 2, patients received 400 mg once-daily oral pralsetinib, and could continue treatment until disease progression, intolerance, withdrawal of consent, or investigator decision. Phase 2 primary endpoints were overall response rate (according to Response Evaluation Criteria in Solid Tumours version 1·1 and assessed by blinded independent central review) and safety. Tumour response was assessed in patients with RET fusion-positive NSCLC and centrally adjudicated baseline measurable disease who had received platinum-based chemotherapy or were treatment-naive because they were ineligible for standard therapy. This ongoing study is registered with ClinicalTrials.gov, NCT03037385, and enrolment of patients with treatment-naive RET fusion-positive NSCLC was ongoing at the time of this interim analysis. Of 233 patients with RET fusion-positive NSCLC enrolled between March 17, 2017, and May 22, 2020 (data cutoff), 92 with previous platinum-based chemotherapy and 29 who were treatment-naive received pralsetinib before July 11, 2019 (efficacy enrolment cutoff); 87 previously treated patients and 27 treatment-naive patients had centrally adjudicated baseline measurable disease. Overall responses were recorded in 53 (61%; 95% CI 50–71) of 87 patients with previous platinum-based chemotherapy, including five (6%) patients with a complete response; and 19 (70%; 50–86) of 27 treatment-naive patients, including three (11%) with a complete response. In 233 patients with RET fusion-positive NSCLC, common grade 3 or worse treatment-related adverse events were neutropenia (43 patients [18%]), hypertension (26 [11%]), and anaemia (24 [10%]); there were no treatment-related deaths in this population. Pralsetinib is a new, well-tolerated, promising, once-daily oral treatment option for patients with RET fusion-positive NSCLC. Blueprint Medicines.
PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data
The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.
Disparities in Lung Cancer Screening in Hispanic Head and Neck Cancer Survivors
Effective cancer screening is essential for early detection and improved survival outcomes. Cancer is a leading cause of death for Hispanics/Latinx, who represent the largest minority group in the U.S. Despite lower tobacco use, lung cancer is the leading cause of cancer death in Hispanic/Latinx men and the second leading cause in women. Late-stage diagnoses, due to limited screening opportunities, contribute to poor survival rates. Cancer survivors, especially those previously diagnosed with head and neck cancer, face a significantly increased risk of developing lung cancer. Approximately one-fourth of head and neck cancer survivors die from a second malignancy, with lung cancer accounting for over half of these cases. These individuals are nearly three times more likely to develop lung cancer compared to the general population of smokers. In this manuscript, we detail the importance of implementing lung cancer screening in these high-risk populations. Plain Language Summary Head and neck cancer survivors are developing lung cancer at much higher incidences than the average population of smokers. Hispanics/Latinx are also dying from LC at a faster rate than any other malignancy. Disparities exist pertaining to the LC survival in both HNC survivors and H/L populations. However, the exact data is unknown given the lack of dedicated studies to understand the behaviors and risk factors of these 2 populations. Therefore, by extrapolating the data for each population separately, we infer that disparities in early detection of LC and the overall LC mortality are higher in these groups combined. To overcome this unmet need, further studies are in dire need to address LCS inequalities in H/L HNC survivors and explore the role of non invasive modalities for LCS.
The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis
Tumor programmed death ligand one (PD-L1) expression has been studied in several trials in non-small-cell lung cancer. We assessed the potential role of PD-L1 expression according to Cochrane Collaboration's Guidelines. 13 studies with 1979 patients were included. Among 915 PD-L1 negative patients this rate was 13% (RR 2.08; 95% CI: 1.49-2.91; p < 0.01). The response rate has increased concurrent to the PD-L1 expression (Pearson's correlation, r = 0.43). PD-L1 expression was also related to better 24-weeks progression-free rate (RR 0.79; 95% CI: 0.71-0.89) and a trend toward better 1-year overall survival rate (RR 0.96; 95% CI: 0.87-1.06). Taking this data in account, PD-L1 overexpression could not be currently considered a robust biomarker to tailor the immune checkpoint inhibitors treatment.
Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States
Purpose Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC). Patients and methods We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results. Results The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third-line therapy. Conclusion Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50 % reduction in the total drug acquisition cost for it to be considered a cost-effective strategy.
Progress and remaining challenges for cancer control in Latin America and the Caribbean
Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.
How Uncommon are Isolated Lung Metastases in Colorectal Cancer? A Review from Database of 754 Patients Over 4 Years
Background It is commonly thought that colon cancer metastases to the lungs without involvement of the liver are rare. Methods We performed a retrospective review of all patients with colorectal cancer diagnosed between December 2003 and August 2007 in Singapore. Isolated lung metastases were determined as (1) Definite if there was confirmed histology or cytology of the lung lesion(s) in the absence of liver lesions on CT scan, and (2) Probable if there were only radiological evidence suggestive of lung metastases rather than lung primary also in the absence of liver lesions on CT scan. Results There were 196 patients with rectal and 558 patients with colon cancer (369 left-sided and 189 right-sided). There were 13 definite isolated lung metastases, and the remaining 43 were probable. Twenty-three (12%) patients with rectal cancer and 33 (6%) patients with colon cancer had isolated lung metastases (OR 2.11, 95% CI 1.21–3.70). Patients with ≥pT3 lesions (OR 1.92, 95% CI 0.75–4.93) and ≥pN1 (OR 1.56, 95% CI 0.86– 2.83) were more likely to have isolated lung metastases. Conclusion The true incidence of isolated lung without liver metastases in colorectal cancer is likely to lie between 1.7% and 7.2%. While the incidence of isolated lung metastases is twice as common in patients with rectal cancer, it is still significant in patients with colon cancer. The absence of liver involvement should not preclude a search for lung metastases.