Characteristics of interstitial lung disease in patients from post-marketing data on metastatic breast cancer patients who received abemaciclib in Japan

Abstract

Background: This study evaluated characteristics of patients treated with abemaciclib and diagnosed with interstitial lung disease (ILD), using 12-month post-marketing data from the real-world setting in Japan.

Methods: Spontaneous reports of adverse events in patients receiving abemaciclib were collected regularly from healthcare providers (HCPs) from November 30, 2018, to November 29, 2019. Detailed follow-up was requested on suspected ILD cases via questionnaires and/or interviews. Radiological images (when available) were reviewed by an ILD adjudication committee of specialists. The age distribution of patients prescribed abemaciclib in Japan was estimated based on insurance claims data.

Results: Of 4700 patients estimated to be exposed to abemaciclib, 82 cases of ILD were reported (46 serious, 13 fatal). Most (91%) had ≥ 1 symptom at diagnosis, commonly dyspnea/shortness of breath (59%), cough (44%), and/or fever (37%). The majority (68%) received steroid therapy (24 [56%] recovered/recovering; 5 [12%] not recovered; 13 [30%] deaths, 1 [2.3%] unknown). No specific imaging patterns or sites of predilection were identified, but a diffuse alveolar damage (DAD) pattern was observed at outcome in 3 of 4 evaluated fatal cases (16 in total evaluated). Features of fatal cases included advanced age, pre-existing interstitial change, and advanced Eastern Cooperative Oncology Group Performance Status.

Conclusion: Advanced age and a DAD pattern were identified as potential risk factors for cases with poorer outcomes, as previously reported for drug-induced ILD. HCPs should consider the benefit-risk profile when prescribing abemaciclib, informing patients of risks and regularly monitoring treated patients to ensure early detection and treatment of ILD.

Keywords: Abemaciclib; Breast cancer; Cyclin-dependent kinase 4/6; Interstitial lung disease.

Fig. 1

Summary of reports of ILD in patients treated with abemaciclib. Data are shown by a ILD reports per month by seriousness; and b ILD onset, representing the time from the first dose of abemaciclib to first imaging study for ILD. The line in (a) shows the cumulative cases of ILD across the monitoring period. ILD, interstitial lung disease

Fig. 2

Outcomes for ILD cases with and without steroid treatment. Steroid pulse treatment included ‘mini-pulse’ treatment (≥ 0.5 g/day of intraveneous methylprednisolone). Pulse transition refers to patients who started on non-pulse steroid therapy but were switched to pulse therapy. F, fatal; ILD, interstitial lung disease; NR, not recovered; R, recovered/recovering; UNK, unknown

Fig. 3

Age distribution of ILD cases and the background population of patients prescribed abemaciclib in Japan. a ILD cases by age and seriousness; b age distribution of abemaciclib-prescribed patients in Japan from insurance claims database

Fig. 4

Radiological findings for ILD in patients treated with abemaciclib. Representative CT images from 4 individual cases which were diagnosed as ILD in patients treated with abemaciclib by the ILD adjudication committee. Days are from first abemaciclib dose. a DAD image pattern showing extensive consolidation in the lower lobe on both sides, which was surrounded by GGO that occupied two-thirds of the lower lobe on both sides. b Non-DAD, faint GGO image pattern showing faint GGO in the whole lung field, which was dominant at the periphery. c OP image pattern beneath pleura at bilateral lower lobe. d NSIP pattern showing an interstitial shadow. CT, computed tomography; DAD, diffuse alveolar damage; ECOG PS, Eastern Cooperative Oncology Group Performance Status; GGO, ground glass opacity; ILD, interstitial lung disease; N, number of cases; NSIP, non-specific interstitial pneumonia; OP, organizing pneumonia. SOB, shortness of breath