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. 2024 Sep 13;24(1):448.
doi: 10.1186/s12890-024-03276-3.

Clinical and radiological pattern of olaparib-induced interstitial lung disease

Alexandre Brudon  1 , Dorine Fournier  2 , Frédéric Selle  3 , Emmanuel Seront  4 , Rosa Conforti  5 , Gwenaëlle Veyrac  6 , Aurore Gouraud  7 , Bénédicte Lebrun-Vignes  2 , Antoine Khalil  8 , Gérard Zalcman  9 , Valérie Gounant  9
Affiliations

Clinical and radiological pattern of olaparib-induced interstitial lung disease

Alexandre Brudon et al. BMC Pulm Med. .

Abstract

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 reaction 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.

Keywords: Adverse effect; Hypersensibility pneumonitis; Interstitial Lung Disease; PARPi.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Index case: Chest CT-scan (CCT). Lung window images on axial transverse CCT were obtained at the right pulmonary artery level, and the coronal-reformatted reconstruction at the carina level. a CCT showing lung quality before olaparib treatment. b Twelve weeks after the beginning of olaparib treatment, CTT showed a diffuse slight high density of the parenchyma. Olaparib was continued. c and d Three weeks later, axial and coronal-reformatted CCT showing a worsening of the parenchyma abnormalities with ground glass opacities associated to areas of lobular hypo-attenuation (arrowheads) and small nodular lesions, with an aspect of hypersensitive pneumonitis. e and f Treatment was stopped and steroid treatment was introduced during three months. The coronal reformatted CCT showed a clear improvement of parenchymal abnormalities with persistence of a small ground glass opacity area to a normal parenchymal appearance
Fig. 2
Fig. 2
Case 2: Chest CT-scan (CCT). Lung window images on axial transverse CCT were obtained at the level of the carina, and the coronal reformatted reconstruction at the level of the superior vena cava. a and b CCT showing lung quality before olaparib treatment. c and d Three months after the beginning of olaparib treatment, CTT showed a lung parenchyma with slight high density related to early ground glass opacities and irregularity of pleural fissure related to thickening of inter-lobules septa (red arrows). e and f One month after the drug was stopped and corticosteroid treatment was started, CCT returned to normal
Fig. 3
Fig. 3
Case 3: Chest CT-scan (CCT). Lung window images on axial transverse CCT and coronal-reformatted reconstruction were obtained at level of the carina. a and b Six weeks after the beginning of olaparib treatment, images on axial transversal and coronal-reformatted CCT showed diffuse bilateral ground glass opacities with a relative respect of lower areas of the lungs and lobular areas of decreased attenuation and vascularisation (arrowheads). c and d After drug was stopped and a week of corticosteroid treatment, axial and coronal reformatted images showed the slow resolution of parenchymal abnormalities with appearance of a subpleural atelectasis band and reverse halo sign (arrows). e and f Two month later, complete disappearance of ground glass opacities and persistence of a sub-pleural atelectasis band on lower lobes were observed
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