Abstract PO1-05-04: CDK4/6 inhibitor-induced Interstitial Lung Disease (ILD) - A Case Series
Authors: Chitalia Ami , Shah Krishna 
Published: May 2024

Abstract
Introduction:
CDK4/6 inhibitors interrupt cell cycle by inhibiting intracellular and hormonal signals responsible for proliferation of malignant cells, making them an effective treatment for patients with HR+ advanced breast cancer. Pre-clinical data demonstrates that CDK4/6 inhibitors allow for inflammatory cell recruitment, inducing pulmonary inflammation and thereby increasing the risk of ILD. The overall risk of ILD was 1.6% in a meta-analysis of over 16,000 patients treated with CDK4/6 inhibitors while individual reported risk was 1%, 1.6% and 3% for palbociclib, ribociclib, and abemaciclib respectively.
Objective:
The aim of this case series is to add to the body of literature about this rare but possibly serious side effect of CDK4/6 inhibitor associated ILD. Early detection and prompt management are essential for improved patient outcomes.
Case 1
A 61 year-old female was diagnosed with metastatic breast cancer to brain and bones after being admitted for evaluation of acute vision loss. She started on palbociclib and letrozole and subsequently had 2 hospitalizations for acute hypoxemic respiratory failure with unremarkable infectious workup. CT scan was significant for bilateral pulmonary infiltrates raising suspicion for CDK4/6 inhibitor-induced pneumonitis; subsequently palbociclib was discontinued and the patient was started on steroid taper resulting in improvement of her respiratory status.
Case 2
A 71 year-old female with a remote history of left breast cancer and sarcoidosis presented with respiratory symptoms. She was found to have metastatic breast cancer with CT scan revealing hilar and mediastinal adenopathy. The patient initially received taxol with near resolution of disease on imaging. The patient was subsequently started on palbociclib + letrozole. After 9 months of treatment, the patient was admitted for pneumonia and discharged home with oxygen. PFTs at the time were suggestive of restrictive pathology related to obesity hypoventilation. Six months later, the patient was admitted for worsening respiratory failure; CT scan revealed interstitial changes likely due to multifactorial etiologies including palbociclib-induced pneumonitis. The patient subsequently passed away.
Case 3
An 81 year-old female diagnosed with remote history of L. breast cancer presented with shortness of breath and weakness. CT scan revealed a nodule and lymphadenopathy; biopsy of nodule was consistent with breast primary. The patient was initially started on ribociclib which was discontinued after 4 cycles due to transaminitis. She was switched to palbociclib, however 2 months after initiation, the patient presented with flu-like symptoms. CT revealed scattered subpleural ground-glass opacities. Infectious workup was negative; pulmonary consultation believed this was likely due to drug-induced pneumonitis and palbociclib was discontinued and she was treated with a steroid taper. Patient was switched to fulvestrant; and after 9 months she was diagnosed with stage IV tongue cancer and her breast cancer therapy was discontinued.
Discussion
CDK4/6 inhibitors have improved survival in patients with metastatic breast cancer, however they are associated with rare but serious adverse effects like ILD. ILD is a challenging clinical diagnosis as it refers to a cluster of disorders of varying presentation and pathophysiology, and as a result can be missed.
Conclusion
This case series demonstrates that CDK4/6 inhibitor-associated ILD may be more prevalent than originally reported. It is important to identify early by performing a thorough workup, including a detailed history and physical exam, medication list review, infectious work-up, chest imaging, PFTs and pulmonology consultation. Publishing a set of standardized guidelines to diagnose and treat CDK4/6 inhibitor-induced ILD is necessary as more cases are identified.

Citation Format: Ami Chitalia, Krishna Shah. CDK4/6 inhibitor-induced Interstitial Lung Disease (ILD) - A Case Series [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-04.