ACUTE ON CHRONIC DYSPNEA IN A PATIENT WITH METASTATIC BREAST CANCER ON ABEMACICLIB

Abstract

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: We report a case illustrating the challenging diagnosis of interstitial pneumonitis caused by abemaciclib in an elderly woman with metastatic breast cancer. Lung toxicity is an uncommon but serious adverse effect of cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors. Diagnosis is typically based on presentation, and non-contrast CT chest is the imaging modality of choice. Typical findings include ground-glass opacities with or without consolidation. The purpose of this case report is to highlight this uncommon toxicity of CDK4/6 inhibitors which requires high level of clinical suspicion for diagnosis. CASE PRESENTATION: A woman in the 8th decade of life with hormone-receptor positive, HER2 negative breast cancer with metastases to lungs and lumbar vertebrae, on treatment with abemaciclib and fulvestrant, was admitted to the hospital for exertional dyspnea for six weeks, with acute worsening to dyspnea at rest in the past one day. Prior to hospitalization, she had developed a fever three weeks after starting abemaciclib. She was treated for community-acquired pneumonia and COPD exacerbation, but had only partial relief of symptoms. CT chest showed ground glass opacities pronounced in right upper and middle lobes, with post-obstructive consolidation in left lower lobe, and soft tissue fullness around the left lower lobe bronchus and along the bronchovascular bundles suspicious for lymphangitic spread of tumor. Upon hospitalization, she was hypoxic and on 3 liters oxygen by nasal cannula. Repeat CT chest showed interval worsening of ground glass opacities in right upper lobe, new ground glass changes in left upper lobe, and worsening of left lower lobe consolidative change. Sputum cultures, fungal studies, and respiratory viral panel were negative. Symptoms improved with initiation of steroids. DISCUSSION: CDK 4/6 inhibitors are a relatively new class of drugs used in tandem with aromatase inhibitors or fulvestrant in the treatment of advanced hormone-receptor positive breast cancer. Diarrhea, nausea, fatigue, and pancytopenia were among common side effects noted in initial clinical trials. For our patient, a steroid course with taper was initiated, and the offending agent was held. A follow up CT scan three months later showed resolution of the ground glass opacities. This approach to management appears to be in line with the limited literature available. CONCLUSIONS: Our case documents an interesting diagnostic challenge in which a patient with developed pneumonitis in the setting of abemaciclib use. The diagnosis was delayed due to comorbid COPD and pneumonia, and confounded by partial resolution in symptoms with antibiotics. In September 2019, the FDA issued a safety warning that abemaciclib, palbociclib, and ribociclib may cause rare but severe pneumonitis. The temporal correlation between initiation of abemaciclib and development of symptoms remains unclear. Reference #1: Corona SP, Generali D. Abemaciclib: A CDK4/6 inhibitor for the treatment of HR+/HEeR2- advanced breast cancer. Drug Des Devel Ther. 2018;12:321-330. doi:10.2147/DDDT.S137783 Reference #2: Johnston S, Martin M, Di Leo A, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. npj Breast Cancer. 2019;5(1):1-8. doi:10.1038/s41523-018-0097-z Reference #3: FDA warns about rare but severe lung inflammation with Ibrance, Kisqali, and Verzenio for breast cancer | FDA. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-severe-lung-inflammation-ibrance-kisqali-and-verzenio-breast-cancer. DISCLOSURES: No relevant relationships by Sameera Natarajan, source=Web Response No relevant relationships by Arjun Natarajan, source=Web Response