Brigatinib for ALK -positive metastatic non-small-cell lung cancer: design, development and place in therapy

Despite the benefits of first and second generation anaplastic lymphoma kinase ( ) inhibitors in the management of -rearranged advanced non-small-cell lung cancer (NSCLC), the development of acquired resistance poses an ongoing dilemma. Brigatinib has demonstrated a wider spectrum of preclinical activity against crizotinib-resistant mutant advanced NSCLC. The current review narrates a brief history of tyrosine kinases, the development and clinical background of brigatinib (including its pharmacology and molecular structure) and its use in -positive NSCLC

Autoimmune haemolytic anaemia in a patient with advanced lung adenocarcinoma and chronic lymphocytic leukaemia receiving nivolumab and intravenous immunoglobulin

We describe a rare case of severe autoimmune haemolytic anaemia (AIHA) in the setting of underlying chronic lymphocytic leukaemia receiving intravenous immunoglobulin, history of warm IgG autoantibody and treatment with nivolumab for advanced non-small cell lung cancer. In this report, we describe AIHA as a potential serious immune-related adverse event from immune checkpoint inhibitors, discuss other potential contributing factors and review previously described cases of AIHA in patients receiving programmed death 1 (PD-1) inhibitors. In the era of immunotherapy, we hope to add literature to raise awareness of potential immune-related sequelae such as AIHA. We aim to highlight the importance of close monitoring for prompt identification and management of potentially fatal AIHA and immune-related adverse events of PD-1 inhibitors by holding immunotherapy and treating with high-dose steroids, particularly in subgroups which may be at increased risk

A radiologic syndrome after high dose chemotherapy and autologous bone marrow transplantation, with clinical and pathologic features of systemic candidiasis

Background. The use of high dose chemotherapy in the treatment of solid tumors is associated with prolonged neutropenia and, consequently, in some patients, systemic candidiasis. The authors describe their experience with a clinicoradiologic syndrome developing after high dose chemotherapy was administered to patients with breast cancer. Methods. The authors evaluated the clinical and radiologic records of 12 patients in whom hepatic, splenic, or renal candidiasis developed. Results. Three patients had positive blood cultures for candida tropicalis. One of these patients and two others had fungal organisms identified with special stains of an organ aspirate. Most patients were asymptomatic, and most of them were treated successfully with antifungal agents, although untreated patients also recovered. There were no fatalities due to the candidiasis. Conclusions. A radiographic syndrome resembling hepatic, splenic, or renal candidiasisis is described, which occurred after high dose chemotherapy was administered and autologous bone marrow transplantation was performed on patients with breast cancer. This syndrome has a favorable prognosis. Conclusions as to the more indolent nature of this syndrome cannot be made; however, this topic warrants further investigation

EGFR Mutation Testing: Changing Patterns of Molecular Testing in Brazil

In Brazil, cancer is the second most common cause of death. Most patients in resource-limited countries are diagnosed in advanced stages. Current guidelines advocate for mutation testing in all patients with metastatic adenocarcinoma. Tyrosine kinase inhibitors are recommended in patients with advanced or metastatic disease harboring sensitizing mutations. In Brazil, there are limited data regarding the frequency of testing and the changes in patterns of testing overtime. This was an observational, retrospective study. We obtained deidentified data from a commercial database, which included 11,684 patients with non-small cell lung cancer treated between 2011 and 2016 in both public and private settings. We analyzed the frequency of mutation testing over time. We also directly studied 3,664 tumor samples, which were analyzed between 2011 and 2013. These samples were tested for mutations through an access program to tyrosine kinase inhibitors in Brazil. Overall, 38% of patients were tested for mutations; 76% of them were seen in the private sector, and 24% were seen in the public center. The frequency of testing for mutations increased significantly over time: 13% (287/2,228 patients) in 2011, 34% (738/2,142) in 2012, 39% (822/2,092) in 2013, 44% (866/1,972) in 2014, 53% (1,165/2,184) in 2015, and 42% (1,359/3,226) in 2016. mutations were detected in 25.5% of analyzed samples (857/3,364). Deletions in Exon 19 were the most frequent mutations, detected in 54% of patients (463/857). Our findings suggest that the frequency of mutation in this cohort was lower than that found in Asia but higher than in North American and Western European populations. The most commonly found mutations were in Exon 19 and Exon 21. Our study shows that fewer than half of patients are being tested and that the disparity is greater in the public sector. These data not only indicate the shortage of testing but also show that the rates of positivity in those tested seem to be higher than in other cohorts for which data have been published. This study further supports the idea that awareness and access to testing should be improved in order to improve survival rates in lung cancer in Brazil