# Impact of everolimus-related interstitial lung disease on subsequent treatment in patients with metastatic breast cancer

**Authors:** Hikari Kiyohara, Chihiro Kondoh, Akira Hirota, Nobuyuki Takahashi, Misao Fukuda, Shota Kusuhara, Takehiko Nakao, Hiromichi Nakajima, Chikako Funasaka, Kenichi Harano, Nobuaki Matsubara, Yoichi Naito, Ako Hosono, Naoki Niikura, Toru Mukohara

PMC · DOI: 10.1093/oncolo/oyag082 · 2026-03-14

## TL;DR

This study examines how lung disease caused by everolimus affects future cancer treatments in breast cancer patients.

## Contribution

The study provides new insights into the impact of everolimus-related lung disease on subsequent treatment choices and outcomes.

## Key findings

- e-rILD did not significantly affect the choice of subsequent anti-cancer treatments.
- The risk of drug-related ILD during subsequent treatments was similar between patients with and without e-rILD.

## Abstract

Everolimus is an option for second-line or later use in combination with endocrine therapy for hormone receptor-positive breast cancer. An important everolimus-associated adverse event is drug-related interstitial lung disease (ILD), reported to occur in 16.0% of individuals in the BOLERO-2 trial, and 23.5% of those in the Asian subgroup. We aimed to examine the impact of everolimus-related ILD (e-rILD) on the risk of drug-related ILD during subsequent anti-cancer treatment.

We retrospectively studied the medical records of patients with metastatic breast cancer treated with everolimus plus endocrine therapy from January 2013 to March 2022, at the National Cancer Center Hospital East. We evaluated e-rILD grade using the Common Terminology Criteria for Adverse Events version 5.0.

A total of 115 cases were treated with everolimus; 33 (28.7%) patients developed e-rILD of any grade, including 5 (15.2%) with grade ≥3 and 2 with grade 5. Management approaches for e-rILD included dose continuation, dose interruption, prednisolone 0.5-1.0 mg/kg, and steroid pulse. The proportions of patients who received subsequent treatment were similar between the e-rILD and no e-rILD groups (73.2% [60/82] vs 81.8% [27/33], respectively; P = .567). Subsequent therapies were generally similar between the 2 groups. Drug-related ILD during regimens following everolimus occurred in one patient (3.7%) with e-rILD and 2 patients (3.3%) without e-rILD (P = .930; odds ratio, 1.12; 95% CI, 0.10-12.86).

e-rILD may not influence the choice of following treatment or the development of drug-related ILD during subsequent treatments.

## Linked entities

- **Chemicals:** everolimus (PubChem CID 6442177), prednisolone (PubChem CID 5755)
- **Diseases:** interstitial lung disease (MONDO:0015925)

## Full-text entities

- **Genes:** PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}
- **Diseases:** visceral (MESH:D007418), hypertension (MESH:D006973), asthenia (MESH:D001247), heart failure (MESH:D006333), Breast cancer (MESH:D001943), Cancer (MESH:D009369), abnormalities in glucose metabolism (MESH:D044882), positive (MESH:D000377), rheumatoid arthritis (MESH:D001172), hormone (MESH:C565870), pancreatic cancer (MESH:D010190), stomatitis (MESH:D013280), diabetes mellitus (MESH:D003920), skin rashes (MESH:D005076), pneumocystis pneumonia (MESH:D011020), toxicity (MESH:D064420), death (MESH:D003643), infectious pneumonia (MESH:D011014), ILD (MESH:D017563), Rare Diseases (MESH:D035583)
- **Chemicals:** Everolimus (MESH:D000068338), gemcitabine (MESH:D000093542), taxanes (MESH:D043823), trastuzumab deruxtecan (MESH:C000614160), steroid (MESH:D013256), fulvestrant (MESH:D000077267), taxane (MESH:C080625), doxorubicin (MESH:D004317), prednisolone (MESH:D011239), capecitabine (MESH:D000069287), docetaxel (MESH:D000077143), giredestrant (MESH:C000720132), exemestane (MESH:C056516), methylprednisolone (MESH:D008775), trastuzumab (MESH:D000068878), paclitaxel (MESH:D017239), CDK4/6 inhibitor (-), anthracycline (MESH:D018943)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13010270/full.md

---
Source: https://tomesphere.com/paper/PMC13010270