1273P - Risk factors for osimertinib-induced interstitial lung disease in patients with metastatic or recurrent non-small cell lung cancer harboring epidermal growth factor receptor mutations

Background

Osimertinib is a standard drug used for treating patients (pts) with metastatic or recurrent non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. However, in real-world settings, it is associated with high incidence of interstitial lung disease (ILD), especially in Japanese pts.

Methods

We conducted a retrospective cohort study on pts treated with osimertinib for metastatic or recurrent NSCLC with EGFR mutations at three institutes in Japan from June 2016 to September 2023. The primary endpoint was incidence of osimertinib-induced ILD. Factors associated with ILD were assessed using the Fine–Gray model.

Results

Among the 347 pts included in the study, 232 (66.9%) and 115 (33.1%) were administered osimertinib as the first- and second-line or later therapy, respectively. Median age of pts was 72 years (range, 33–90), and 143 (41.2%) pts were aged over 75 year. Interstitial lung abnormality (ILA) at baseline was observed in 11 (3.1%) pts. The overall incidence of ILD was 61 (17.6 %). Among the pts with ILD, 29 (47.5%) had grade 1 and 32 (52.5%) had grade 2 or higher ILD. The incidence of ILD was significantly higher in pts with low body surface area (BSA) (<1.48 m²) (n = 40, 26.8%) than in those with high BSA (n = 21, 10.6%, p < 0.001). Moreover, the incidence of ILD was significantly higher in older pts (n = 37) than in younger pts (n = 24) (25.9% vs. 11.8%, p < 0.001). First-line treatment with osimeritinb (n = 49) was associated with higher incidence of ILD than the other treatment lines (n = 12) (21.1% vs. 10.4%, p = 0.016). Multivariate analysis revealed older age (hazard ratio [HR], 1.83, 95% confidence interval [CI], 1.06–3.16, p = 0.03), low BSA (HR, 2.7, 95%CI, 1.35–5.39, p = 0.0049), presence of ILA (HR, 4.89, 95% CI, 2.43–9.81, p < 0.001), and first-line treatment with osimertinib (HR, 2.43, 95% CI, 1.29–4.58, p = 0.0059) as risk factors for osimertinib-induced ILD.

Conclusions

Old age, low BSA, presence of ILA, and first-line treatment with osimertinib are associated with increased incidence of osimertinib-induced ILD. These findings would be useful in mitigating the ILD risk associated with osimertinib therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Hase: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Eli Lilly Japan, Takeda Pharmaceutical, Taiho Pharmaceutical, Merck BioPharma, MSD, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, Novartis Pharma, Chugai Pharmaceutical, AbbVie, BeiGene, Amgen; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical, Nippon Boehringer Ingelheim. All other authors have declared no conflicts of interest.