Interstitial lung disease and CDK4/6 inhibitors in the treatment of breast cancer

ABSTRACT

Introduction

CDK4/6 inhibitors have changed the treatment paradigm of many patients living with metastatic and early-stage high-risk hormone receptor (HR)-positive breast cancer. Even though patients and clinicians are aware and learning how to manage common adverse events, such as bone marrow suppression and gastrointestinal toxicities, there are less common and potentially severe adverse events, such as interstitial lung disease (ILD), that require special consideration.

Areas covered

In this narrative review, we discuss the incidence, mechanism, and treatment of CDK4/6 inhibitor associated ILD.

Expert opinion

CDK4/6 inhibitors in combination with endocrine therapy (ET) are standard treatment for HR-positive, HER2-negative metastatic breast cancer and for selected patients with early stage HR-positive breast cancer. Common toxicities of these medications are often controlled with dose reductions, dose interruptions, and/or prophylactic medications, such as antidiarrheals. However, there are a small subset of patients at risk for less common and potentially severe toxicities, such as ILD. Individualized risk should be considered, including underlying lung disease, thrombosis risk and drug-drug interactions, in order to counsel patients about the risk of ILD.

KEYWORDS:

• Abemaciclib
• breast cancer
• CDK4/6 inhibitors
• lung disease
• palbociclib
• pneumonitis
• ribociclib

Article highlights

• Three CDK4/6 inhibitors, in combination with endocrine therapy, are the preferred first-line treatment for patients with metastatic hormone receptor (HR)-positive, HER2-negative disease.

• In addition to bone marrow suppression and gastrointestinal toxicities, there are less common and potentially severe adverse events, such as interstitial lung disease (ILD), that require special consideration.

• The incidence of CDK4/6 inhibitor associated ILD is 1–2%. Since ILD has clinically broad and nonspecific presentation, a high level of suspicion is needed to diagnose and treat patients promptly.

• For patients with pulmonary disease, the use of CDK4/6 inhibitors is not absolutely contraindicated. The severity of the underlying condition must be considered in patients with high risk of toxicity. Patient education and shared decision making are critical.

Declaration of interest

SM Tolaney reports consulting or advisory role for Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi-Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Artios Pharma, Menarini/Stemline, Aadi Biopharma, Bayer, Incyte Corp, and Jazz Pharmaceuticals; and institutional research support from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, NanoString Technologies, Seattle Genetics, and OncoPep. A Giordano reports participating on the Pfizer Advisory Board this year.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Acknowledgments

We thank Valerie Hope Goldstein for editing and submission assistance. She is a full-time employee of Dana-Farber Cancer Institute.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2288147

Additional information

Funding

This paper was not funded.