JAMA oncology
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Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti-programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). ⋯ High rates of response to first-line avelumab therapy in patients with distant mMCC build on previously reported antitumor activity after second-line or later treatment, and maturing progression-free survival data suggest that responses are durable. These data further support avelumab's approval in the United States and European Union and use as a standard-of-care treatment for mMCC.
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Multicenter Study
Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial.
Treatment options for patients with disease progression after treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1) are limited. Tucatinib is an oral, potent, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel treatment for ERBB2/HER2-positive breast cancer. ⋯ In this study, tucatinib in combination with T-DM1 appeared to have acceptable toxicity and to show preliminary antitumor activity among heavily pretreated patients with ERBB2/HER2-positive metastatic breast cancer with and without brain metastases.
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Identification of patients with hereditary renal cell carcinoma (RCC) is important for cancer screening and, in patients with advanced disease, for guiding treatment. The prevalence of cancer-related germline mutations in patients with advanced RCC and the phenotypes associated with some rare mutations are unknown. ⋯ Of patients with non-clear cell RCC, more than 20% had a germline mutation, of which half had the potential to direct systemic therapy. Current referral criteria for genetic testing did not identify a substantial portion of patients with mutations, supporting the role of a more inclusive sequencing approach.
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Stereotactic body radiation therapy (SBRT) has become a standard treatment for patients with medically inoperable early-stage lung cancer. However, its effectiveness in patients medically suitable for surgery is unclear. ⋯ As given, SBRT appears to be associated with a high rate of primary tumor control, low treatment-related morbidity, and infrequent need for surgical salvage in patients with operable early-stage lung cancer.
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Multicenter Study
Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study.
Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity. ⋯ Isocitrate dehydrogenase differentiation syndrome is a recognizable and potentially lethal clinical entity, occurring in approximately 12% of enasidenib-treated patients with mutant-IDH2 R/R AML. It requires prompt recognition and management. As use of mutant IDH inhibitors increases, these findings and recommendations are increasingly germane to care of patients with mutant-IDH neoplasms.