Clinical and radiological pattern of olaparib- induced interstitial lung disease

Background: PARP inhibitors (PARPi) are used in the treatment of ovarian, breast, pancreatic, and prostate cancers. Pneumonitis has been identified as a potential side effect, with a higher meta-analysis-assessed risk for olaparib versus other PARPi. Olaparib-induced interstitial lung disease (O-ILD) was first described within the Japanese population, with few information available for Caucasian patients. Methods: We performed a retrospective study by pooling data from the French and Belgian pharmacovigilance databases from 2018 to 2022. Patients with O-ILD were included following a central review by: 1) pharmacologists using the French drug causality assessment method; 2) senior pneumologists or radiologists, using the Fleischner Society’s recommendations. Results: Five patients were identified and analysed. All were females, with ovarian or breast cancer. Median age at O-ILD diagnosis was 71 (38-72) years old, with no smoking history. Median delay between treatment initiation and symptom occurrence was 12 (6-33) weeks. Pneumonitis severity assessed using the Common Terminology Criteria for Adverse Events V5 was Grade 3 (n=4) or 2 (n=1). CT-scan review (n=3) described hypersensitivity pneumonitis as a common pattern. Bronchioalveolar lavage (n=4) revealed lymphocytic alveolitis. Treatments relied on olaparib discontinuation (n=5) and glucocorticoid intake (n=4), with no fatal issue. Safe re-challenge with PARPi occurred in two patients. Forty additional O-ILD cases were identified in the WHO VigiBase database, including one fatal case. Conclusions: PARPi-ILD is a rare but potentially life-threatening disease, presenting as a hypersensitivity pneumonitis pattern within 3 months of PARPi initiation. Treatment primarily relies on medication discontinuation. Re-challenging with another PARPi could be considered. Clinical trial number : CEPRO #2023-010