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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.

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., Competing Interests: Maurício Fernando Silva Almeida RibeiroTravel, Accommodations, Expenses: Foundation Medicine Rodrigo Medeiros BovolinStock and Other Ownership Interests : Abbott Laboratories (ABT), Johnson & Johnson (JNJ), Novo Nordisk A/S (NVO), Edwards Lifesciences (EW), Zoetis Inc (ZTS), Gilead Sciences (GILD), Varian Medical Systems Inc. (VAR), Varex Imaging Corporation (VREX) Fernando Costa SantiniHonoraria: Merck Sharp & Dohme, Roche, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, Wyeth, AmgenConsulting or Advisory Role: Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Roche, Bayer, Lilly, AmgenSpeakers' Bureau: Roche, Merck Sharp & Dohme, AstraZeneca, BayerTravel, Accommodations, Expenses: Bayer, Merck Sharp & Dohme, Bristol Myers Squibb Rodrigo Ramella MunhozHonoraria: Bristol Myers Squibb, MSD, Roche, Novartis, Sanofi, Merck SeronoConsulting or Advisory Role: Roche, Merck Serono, Sanofi, Bristol Myers SquibbSpeakers' Bureau: Bristol Myers Squibb, MSD, Novartis, RocheResearch Funding: Lilly, Roche, Bristol Myers Squibb, Novartis, MSDTravel, Accommodations, Expenses: Bristol Myers Squibb, MSD, Roche, Sanofi Denis Leonardo Fontes JardimHonoraria: Janssen-Cilag, Roche/Genentech, Astellas Pharma, MSD Oncology, BMS Brazil, Pfizer, Libbs, MerckConsulting or Advisory Role: Janssen-Cilag, Pfizer, MSDTravel, Accommodations, Expenses: MSD, BMS Brazil, Janssen-Cilag Gustavo dos Santos FernandesHonoraria: Roche, MSD Oncology, BayerResearch Funding: Roche, Memorial Sloan-Kettering Cancer Center, BMS BrazilTravel, Accommodations, Expenses: Roche Maria Isabel AchatzConsulting or Advisory Role: RocheSpeakers' Bureau: AstraZeneca, MSD Oncology, Merck Sharpe & DohmeNo other potential conflicts of interest were reported.

Selpercatinib, a novel, highly selective and potent, inhibitor of RET , demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pretreated and treatment-naive RET fusion-positive non-small-cell lung cancer patients in a Phase I/II clinical trial. LIBRETTO-431 (NCT04194944) is a randomized, global, multicenter, open-label, Phase III trial, evaluating selpercatinib versus carboplatin or cisplatin and pemetrexed chemotherapy with or without pembrolizumab in treatment-naive patients with locally advanced/metastatic RET fusion-positive nonsquamous non-small-cell lung cancer. The primary end point is progression-free survival by independent review. Key secondary end points include overall survival, response rate, duration of response and progression-free survival. Clinical trial registration: NCT04194944 (ClinicalTrials.gov).

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., Competing Interests: Dr de Castro Junior reports personal fees and other from AstraZeneca, personal fees and other from Roche, personal fees and other from Boehringer-Ingelheim, outside the submitted work. The other authors declare that they have no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine-related irAEs. Current data from clinical trials show increased incidence of hypophysitis with CTLA4 inhibition and thyroid dysfunction with PD-(L)1 blockade. In addition, a few cases of type 1 diabetes mellitus and primary adrenal insufficiency have been reported. We discuss the incidence, clinical manifestations, diagnosis and management of immune-related endocrinopathies in this highly complex context of oncological patients in need of immunotherapies., (© 2017 Society for Endocrinology.)