Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.

Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome.

PURPOSE: Li-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of carrying the Brazilian founder mutation because of its lower penetrance and variable expressivity. This variant is rarely described in databases of somatic mutations. Somatic findings in tumor molecular profiling may give insight to identify individuals who might be carriers of LFS and allow the adoption of risk reduction strategies for cancer. MATERIALS AND METHODS: We determined the frequency of the TP53 p.R337H variant in tumor genomic profiling from 755 consecutive Brazilian patients with pan-cancer. This is a retrospective cohort from January 2013 to March 2020 at a tertiary care center in Brazil. RESULTS: The TP53 p.R337H variant was found in 2% (15 of 755) of the samples. The mutation allele frequency ranged from 30% to 91.7%. A total of seven patients were referred for genetic counseling and germline testing after tumor genomic profiling results were disclosed. All the patients who proceeded with germline testing (6 of 6) confirmed the diagnosis of LFS. Family history was available in 12 cases. Nine patients (9 of 12) did not meet LFS clinical criteria. CONCLUSION: The identification of the TP53 p.R337H variant in tumor genomic profiling should be a predictive finding of LFS in the Brazilian population and should prompt testing for germline status confirmation.

TRK Inhibitors in Non-Small Cell Lung Cancer.

OPINION STATEMENT: Care should be taken to ensure that the diagnostic strategy for a recently diagnosed advanced non-small cell lung cancer includes NTRK fusion testing. RNA sequencing is the gold standard method of detection of NTRK fusion; however, pan-TRK immunohistochemistry could be used as a screening method with good sensitivity. Larotrectinib and entrectinib are approved therapies for TRK fusion-positive lung cancers as first or subsequent lines of therapy. TRK inhibition has demonstrated clinically meaningful, deep, and durable systemic and central nervous system responses. Larotrectinib and entrectinib have a manageable safety profile, including some TRK-related adverse events, such as dizziness and weight gain. At disease progression on first-generation TRK inhibitors, enrollment on a clinical trial should be encouraged, as new-generation TRK inhibitors are being tested.

Successful osimertinib rechallenge following drug-induced pneumonitis after previous anti-PDL1 exposure.

Osimertinib is a first-line treatment option for patients with metastatic non-small cell lung cancer (NSCLC) harbouring EGFR mutations. Pneumonitis is a severe adverse event (AE) related to osimertinib treatment which appears to be more frequent when associated with concurrent or previous anti-PD(L)1 exposure. Data regarding the efficacy and safety of osimertinib rechallenge, especially in the setting of central nervous system (CNS) metastases, are scarce. We herein describe a case of a 53-year-old patient with metastatic EGFR-mutated NSCLC, who developed pneumonitis after osimertinib treatment and was successfully rechallenged with 40 mg daily osimertinib, with CNS response. This dose reduction strategy may be an option for selected patients with brain metastases after tyrosine kinase inhibitors-induced AEs.