To Crush or Not to Crush: Administering Dabrafenib and Trametinib Through a Nasogastric Tube in a Critically Ill Patient With Nonsmall Cell Lung Cancer - A Case Report and Review of Literature of Targeted Therapies Given Through Enteral Feeding Tubes.

Up to 71% of lung cancer patients admitted to the ICU are newly diagnosed. The decision to initiate cancer directed treatments in lung cancer patients admitted to the ICU remains complex. For those with identified oncogene driver mutations, targeted therapies with rapid and high response rates are attractive treatment options. However, mechanically ventilated patients face additional barriers in which enteral tube administration of oral therapies may require tablets or capsules to be crushed or opened and diluted. Data on the pharmacodynamics and pharmacokinetics of this alternative route of administration are often very limited. Here we describe the first case report of an intubated patient with newly diagnosed NSCLC who was successfully treated with opened dabrafenib capsules and crushed trametinib tablets administered through a nasogastric tube. We also provide a review of the existing literature on feeding tube administration of commonly used tyrosine kinase inhibitors in lung cancer. Tyrosine kinase inhibitors administered through feeding tubes can lead to a clinically meaningful recovery in critically ill patients.

Combinatorial therapy is a safe and durable treatment option in ALK-rearranged non-small cell lung cancer with an acquired MET exon 14 skipping mutation mediated resistance to alectinib: a case report.

Background: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are standard first line treatment for ALK-rearranged non-small cell lung cancer (NSCLC) and have demonstrated high and durable response rates. Despite these initial responses, patients eventually develop resistance through ALK dependent and ALK independent alterations. These resistance mechanisms have made treatment decisions increasingly more complex. Here we describe a case of an acquired mesenchymal epithelial transition factor (MET) exon 14 skipping (METex14) mutation mediated resistance to alectinib in a patient with ALK-rearranged lung adenocarcinoma. Case Description: We present a 72-year-old male with a 2-pack year smoking history and end-stage renal disease on hemodialysis diagnosed with metastatic lung adenocarcinoma harboring an echinoderm microtubule-associated protein 4 (EML4)-ALK fusion gene mutation. The patient was initially treated with alectinib with good response. However, the patient eventually developed resistance. Next generation sequencing of a liquid biopsy at time of progression revealed a MET exon 14 skip mutation. The patient was started on dual alectinib and capmatinib therapy, which led to a rapid and durable response. Conclusions: This is the first case report of the successful treatment of METex14 mutation mediated resistance to alectinib with combination therapy of alectinib and capmatinib, which led to a rapid and durable response in our patient. This case highlights the importance of resequencing patients at the time of progression to identify potential actionable ALK dependent and independent resistance alterations. Combinatorial therapy may provide a promising effective and safe therapy option for patients who acquire resistance after initial TKI therapy.

Hypocomplementemic Urticarial Vasculitis Syndrome Masquerading as Systemic Lupus Erythematosus: A Case Report.

Introduction: Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an infrequent immune complex-mediated condition characterized by nonpruritic urticarial lesions, low serum complement levels, and autoantibodies, associated with systemic manifestations like arthralgia/arthritis, angioedema, ocular inflammation with conjunctivitis, episcleritis, uveitis, renal, gastrointestinal, and pulmonary involvement. HUVS and systemic lupus erythematosus (SLE) overlap and the criteria for identifying HUVS as an entity distinct from SLE are lacking. Despite the diagnostic criteria established by Schwartz et al. [Curr Opin Rheumatol. 2014;26(5):502-9], differentiation from SLE is sometimes difficult as patients often also fulfill the classification criteria of the American College of Rheumatology (ACR). The prognosis of HUVS depends on the organ system involved. Lung disease results in significant morbidity and mortality and is made worse by smoking. Kidney involvement with glomerulonephritis may ultimately result in end-stage renal disease with the need for kidney transplant. Death may also occur due to acute laryngeal edema. Case Presentation: We pre-sent a case of a 40-year-old female who had a diagnosis of SLE, presented with severe odynophagia, was found to have an erythematous macular rash, and had acute kidney injury attributed to contrast-related injury and cardiorenal syndrome. After the resolution of the AKI, she continued to have hematuria and low-grade proteinuria that led to a kidney biopsy that aided in the diagnosis of HUVS. Discussion/Conclusion: Given the rarity of this disease and the difficulty in differentiating HUVS from other rheumatological diseases such as SLE, further accumulation of cases is necessary to understand the best diagnostic modality for this entity.