Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: Tafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed "radical cure." METHODS: We performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy. The trial was conducted at seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand and involved patients with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and female patients with moderate G6PD enzyme deficiency; all patients had confirmed P. vivax parasitemia. The patients were randomly assigned, in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision); all patients received a 3-day course of chloroquine and were followed for 180 days. The primary safety outcome was a protocol-defined decrease in the hemoglobin level (>3.0 g per deciliter or ≥30% from baseline or to a level of <6.0 g per deciliter). Freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficacy outcome in a planned patient-level meta-analysis of the current trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations), and an odds ratio for recurrence of 1.45 (tafenoquine vs. primaquine) was used as a noninferiority margin. RESULTS: A protocol-defined decrease in the hemoglobin level occurred in 4 of 166 patients (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 patients (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group, for a between-group difference of 1.2 percentage points (95% CI, -4.2 to 5.0). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% (95% CI, 61.0 to 72.3) among the 426 patients in the tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among the 214 patients in the primaquine group. The efficacy of tafenoquine was not shown to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96). CONCLUSIONS: Among patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P. vivax malaria, although tafenoquine was not shown to be noninferior to primaquine. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; GATHER ClinicalTrials.gov number, NCT02216123 .).

Impact of COVID-19 Infection on Patients with Cancer: Experience in a Latin American Country: The ACHOCC-19 Study.

INTRODUCTION: The ACHOCC-19 study was performed to characterize COVID-19 infection in a Colombian oncological population. METHODOLOGY: Analytical cohort study of patients with cancer and COVID-19 infection in Colombia. From April 1 to October 31, 2020. Demographic and clinical variables related to cancer and COVID-19 infection were collected. The primary outcome was 30-day mortality from all causes. The association between the outcome and the prognostic variables was analyzed using logistic regression models and survival analysis with Cox regression. RESULTS: The study included 742 patients; 72% were >51 years. The most prevalent neoplasms were breast (132, 17.77%), colorectal (92, 12.34%), and prostate (81, 10.9%). Two hundred twenty (29.6%) patients were asymptomatic and 96 (26.3%) died. In the bivariate descriptive analysis, higher mortality occurred in patients who were >70 years, patients with lung cancer, ≥2 comorbidities, former smokers, receiving antibiotics, corticosteroids, and anticoagulants, residents of rural areas, low socioeconomic status, and increased acute-phase reactants. In the logistic regression analysis, higher mortality was associated with Eastern Cooperative Oncology Group performance status (ECOG PS) 3 (odds ratio [OR] 28.67; 95% confidence interval [CI], 8.2-99.6); ECOG PS 4 (OR 20.89; 95% CI, 3.36-129.7); two complications from COVID-19 (OR 5.3; 95% CI, 1.50-18.1); and cancer in progression (OR 2.08; 95% CI, 1.01-4.27). In the Cox regression analysis, the statistically significant hazard ratios (HR) were metastatic disease (HR 1.58; 95% CI, 1.16-2.16), cancer in progression (HR 1.08; 95% CI, 1.24-2.61) cancer in partial response (HR 0.31; 95% CI, 0.11-0.88), use of steroids (HR 1.44; 95% CI, 1.01-2.06), and use of antibiotics (HR 2.11; 95% CI, 1.47-2.95). CONCLUSION: In our study, patients with cancer have higher mortality due to COVID-19 infection if they have active cancer, metastatic or progressive cancer, ECOG PS >2, and low socioeconomic status. IMPLICATIONS FOR PRACTICE: This study's findings raise the need to carefully evaluate patients with metastatic cancer, in progression, and with impaired Eastern Cooperative Oncology Group status to define the relevance of cancer treatment during the pandemic, consider the risk/benefit of the interventions, and establish clear and complete communication with the patients and their families about the risk of complications. There is also the importance of offering additional support to patients with low income and residence in rural areas so that they can have more support during cancer treatment.

Real-world evidence of nivolumab for non-small-cell lung cancer in a developing country.

Nivolumab is a human programmed death receptor-1 blocking antibody, used as treatment option in patients with advanced non-small-cell lung cancer (NSCLC). We assessed the nivolumab efficacy in terms of survival and response to treatment as second-line (2L) or third-line (3L) therapy in patients with advanced NSCLC. This is a multicentric observational study. Data of patients with advanced NSCLC who received nivolumab as 2L or 3L treatment were analyzed retrospectively. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness, and safety of nivolumab treatment were collected. The outcomes evaluated were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) to treatment. OS and PFS were estimated with the Kaplan-Meier method and the differences were evaluated through the log-rank test. Data of 178 patients were included. The median follow-up was 26.8 months (interquartile range (IQR): 20.3-40.4). Nivolumab was commonly used as a 2L treatment (77.5%). The outcomes in this setting (2L) were as follows: ORR was 21.0%, and the median PFS and OS were 5.5 months (95% confidence interval (CI): 4.5-6.5) and 12.4 months (95% CI: 10.8-14.0), respectively. In 3L, the ORR with nivolumab was 15.0%, the median PFS and OS were 4.1 months (95% CI: 3.1-5.1) and 10.1 months (95% CI: 9.4-10.6), respectively. Three patients (1.7%) required discontinuation due to toxicity. Nivolumab effectiveness and safety in this scenario was consistent with that reported by previous trials and other real-world data.

Impact of vaccination against COVID-19 on patients with cancer in ACHOC-C19 study: Real world evidence from one Latin American country.

Introduction: During the pandemic, it has been recommended that vaccination against COVID-19 be a priority for patients with cancer; however, these patients were not included in the initial studies evaluating the available vaccines. Objective: To define the impact of vaccination against COVID-19 in preventing the risk of complications associated with the infection in a cohort of patients with cancer in Colombia. Methods: An analytical observational cohort study, based on national registry of patients with cancer and COVID 19 infection ACHOC-C19, was done. The data was collected from June 2021, until October 2021. Inclusion criteria were: Patients older than 18 years with cancer diagnosis and confirmed COVID-19 infection. Data from the unvaccinated and vaccinated cohorts were compared. Outcomes evaluated included all-cause mortality within 30 days of COVID-19 diagnosis, hospitalization, and need for mechanical ventilation. The estimation of the effect was made through the relative risk (RR), the absolute risk reduction (ARR) and the number needed to treat (NNT). Multivariate analysis was performed using generalized linear models. Results: 896 patients were included, of whom 470 were older than 60 years (52.4%) and 59% were women (n=530). 172 patients were recruited in the vaccinated cohort and 724 in the non-vaccinated cohort (ratio: 1 to 4.2). The cumulative incidence of clinical outcomes among the unvaccinated vs vaccinated patients were: for hospitalization 42% (95% CI: 38.7%-46.1%) vs 29%; (95% CI: 22.4%-36.5%); for invasive mechanical ventilation requirement 8.4% (n=61) vs 4.6% (n=8) and for mortality from all causes 17% (n=123) vs 4.65% (n=8). Conclusion: In our population, unvaccinated patients with cancer have an increased risk of complications for COVID -19 infection, as hospitalization, mechanical ventilation, and mortality. It is highly recommended to actively promote the vaccination among this population.

Real-world evaluation of molecular testing and treatment patterns for EGFR mutations in non-small cell lung cancer in Latin America.

Lung cancer is a leading cause of cancer-related deaths in Latin America, with non-small cell lung cancer (NSCLC) being the most prevalent. The current study aimed to report real-world data on epidermal growth factor receptor (EGFR) mutational testing and treatment regimens at diagnosis and progression in patients with metastatic NSCLC across four Latin American countries (Argentina, Chile, Colombia and Uruguay). A retrospective, multicenter, observational study was conducted in patients with NSCLC using medical records from participating countries. The study population was categorized into two cohorts: Cohort 1 comprised of newly diagnosed, treatment-naïve patients with stage IV NSCLC; and cohort 2 comprised of stage IV NSCLC EGFR mutation (EGFRm)-positive patients who had progressed after first- or second-generation EGFR-tyrosine kinase inhibitor (TKI) treatment. Measures included demographic variables, health characteristics, treatment regimen, molecular testing rate and turnaround time at diagnosis and at progression for cohorts 1 and 2, respectively. Descriptive statistics were used to summarize all study measures. Of the 462 patients enrolled, 431 were newly diagnosed or treatment naïve with metastatic NSCLC. In cohort 1, the majority of patients with private health insurance (57.31%) underwent molecular diagnosis while only 41.3% of patients within the public sector had access to testing. The average molecular testing rate in cohort 1 varied across countries, with Argentina having the highest testing rate (79%) and Uruguay the lowest (27.63%). EGFRm was observed in 22% of patients. Cohort 2 comprised 31 patients who had progressed after first- or second-generation EGFR-TKI treatment and of these, only 22 (70.97%) underwent testing after progression. Access to molecular testing is still a challenge impacting the choice of first-line treatment in Latin American patients with NSCLC. These findings underline the unmet needs of ensuring early diagnosis, molecular profiling and use of correct treatment to alleviate NSCLC burden in the region.

Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach.

Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.

Condroma del espacio parafaríngeo, reporte de un caso / Chondroma of the parapharyngeal space, report of one case

Introducción. El condroma es una neoplasia benigna de origen mesenquimal y de etiología desconocida, muy infrecuente en los tejidos blandos debido a su constitución de células de cartílago maduro sin hueso; sin embargo, son frecuentes las calcificaciones focales. Al presentarse en cabeza y cuello, suele hacerlo en el maxilar o el paladar duro, y son pocos los reportes de este tumor en el espacio parafaríngeo. Se reporta el caso de una paciente de 68 años de edad, que acudió a consulta por dolor en el paladar blando, cefalea y dolor paratiroideo izquierdo asociado a disfagia de cuatro años de evolución. Se practicaron los estudios pertinentes y, finalmente, se confirmó el diagnóstico de condroma mediante biopsia. Discusión. Los condromas muy rara vez se encuentran en los tejidos blandos, por lo cual se sugiere que el diagnóstico sea cuidadosamente orientado para descartar una posible malignidad de la lesión y que los controles posquirúrgicos sean frecuentes

Introduction: Chondroma is a benign neoplasm of mesenchymal origin and of unknown etiology, very infrequently appearing in the soft tissues due to its constitution of mature cartilage cells without bone; however, they usually present focal calcifications. When occurring in the head and neck, they usually appear in the jaw or hard palate. Just a few cases of this pathology are reported in the pharynx. Materials and Methods: We present a case of a female 68 years old, who came to the clinic due to pain in the soft palate, headache and left parathyroid pain associated with dysphagia, of four years of evolution. Corresponding studies were carried out and finally the diagnosis of chondroma was confirmed by biopsy. Discusion: Chondromas are rarely found in the soft tissues, suggesting that the diagnosis should be carefully oriented to rule out possible malignancy of the lesion and that post-surgical controls should be frequent