The oncologist
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On August 30, 2017, the U. S. Food and Drug Administration approved Actemra (tocilizumab, Genentech, Inc., South San Francisco, CA) for the treatment of severe or life-threatening chimeric antigen receptor (CAR) T cell-induced cytokine release syndrome (CRS) in adults and in pediatric patients 2 years of age and older. ⋯ Thirty-one patients (69%; 95% confidence interval, 53%-82%) achieved a response as defined. In an independent cohort of 15 patients with KTE-C19-induced CRS, 53% responded. Further study is needed to determine the optimal dose of tocilizumab and to confirm the safety of its use for treatment of patients with CAR T cell-induced CRS.
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Immune checkpoint inhibitors (ICIs) are approved for a wide range of malignancies. They work by priming the immune system response to cancer and have changed the landscape of available cancer treatments. As anticipated, modulation of the regulatory controls in the immune system with ICIs results in diverse immune-related adverse events, targeting any organ or gland. ⋯ Currently, there are no clear guidelines for surveillance, diagnosis, or management of this entity. There are multiple unresolved issues including, but not limited to, identifying those at risk of this uncommon toxicity, elucidating the pathophysiology, determining if and what type of surveillance is appropriate, optimal work-up of suspected patients, and methods for resolution of myocarditis. Here we describe a clinical vignette and discuss the salient features and management strategies of ICI-associated myocarditis.
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The incidence and mortality rate of colorectal cancer (CRC) have increased dramatically over the past 3 decades in China due to changes in lifestyle factors. Early detection and treatment guidelines for asymptomatic cases have shown to improve CRC control in developed countries. In response to these challenges, the Shanghai Municipal Government launched a community-based CRC screening program in 2012. ⋯ Due to socioeconomic transitions and lifestyle changes, colorectal cancer is now becoming one of the most common cancers in developing countries, as it is in developed countries. While most developed countries have now initiated national colorectal cancer screening programs based on recommended country-specific colorectal cancer screening guidelines, colonoscopy has become the most commonly used screening method. This is a challenge in developing countries due to limited resources. Based on the analysis of the Shanghai colorectal cancer screening program, with immunological fecal occult blood test and risk assessment as initial screening, followed by a diagnostic testing of colonoscopy for individuals with positive results, this article provides the basis and suggestion for similar program in other regions of China and other developing countries.
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Rare cases of severe myocarditis are reported during treatment with nivolumab. Troponin, a biomarker of cardiac damage, is a key component of the diagnostic workup of many cardiac disorders, including myocarditis. This study investigates the role of troponin to assess cardiac involvement during nivolumab therapy for non-small cell lung cancer (NSCLC). ⋯ Myocarditis is a rare but serious adverse event of immune checkpoint blockade with nivolumab, which needs to be recognized as soon as possible. This article suggests that troponin, a user-friendly biomarker of myocardial cytotoxicity, might be useful for early detection of immune-mediated myocarditis. However, because troponin abnormalities might also be related to a number of conditions capable of causing myocardial oxygen demand-supply mismatch, a careful cardiac assessment should be performed in non-small cell lung cancer patients in order to properly interpret any troponin increase. According to the available evidence, monitoring troponin during the first weeks of treatment can be considered reasonable.
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On June 22, 2017, the Food and Drug Administration expanded indications for dabrafenib and trametinib to include treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring BRAF V600E mutations. Approval was based on results from an international, multicenter, multicohort, noncomparative, open-label trial, study BRF113928, which sequentially enrolled 93 patients who had received previous systemic treatment for advanced NSCLC (Cohort B, n = 57) or were treatment-naïve (Cohort C, n = 36). All patients received dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily. ⋯ S. electronic health records at two academic sites, characterizing treatment outcomes data for patients with metastatic NSCLC with or without BRAF V600E mutations. The treatment effect of dabrafenib 150 mg twice daily was evaluated in 78 patients with previously treated BRAF mutant NSCLC, yielding an ORR of 27% (95% CI 18%-38%), establishing that dabrafenib alone is active, but that the addition of trametinib is necessary to achieve an ORR of >40%. The most common adverse reactions (≥20%) were pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.