Osimertinib rechallenge under steroid protection following osimertinib-induced pneumonitis: three case studies

Abstract

Osimertinib is a third-generation tyrosine kinase inhibitor that became the preferred first-line treatment option for metastatic non-small cell lung cancer with sensitizing epidermal growth factor receptor mutations. Drug-induced pneumonitis is known to occur with osimertinib. In case of severe pneumonitis, discontinuation of treatment and therapy with corticosteroids is recommended, and a treatment switch is usually performed. We herein report the treatment course in three patients who were rechallenged with osimertinib under steroid protection following an osimertinib-induced pneumonitis. All our patients were initially re-exposed to a lower dose of osimertinib. Two patients were successfully rechallenged under prednisolone protection. The third patient, who was initially retreated with osimertinib without steroid protection, suffered from a recurrent pneumonitis, and was later rechallenged successfully under steroid protection. Our case series indicates that rechallenge with osimertinib following recovery from osimertinib-induced pneumonitis allows a successful rechallenge in individual cases when alternative treatment options are lacking. Concomitant steroids appear to protect against flares of pneumonitis during rechallenge.

Successful administration of low-dose almonertinib in a patient with lung adenocarcinoma after osimertinib-induced interstitial lung disease: a case report and literature review

“…Therefore, timely intervention is very important. The majority of reported cases, including our case, successfully controlled OsiILD by discontinuing or reducing osimertinib and treating it with corticosteroids [ 5 , 15 , 27 , 28 , 30 , 32 – 35 , 37 , 38 ]. It has also been reported that OsiILD can be successfully controlled by nintedanib [ 36 ], so the use of nintedanib to control OsiILD can be considered in patients who are not suitable for corticosteroid therapy.…”

“…In several cases about OsiILD reported so far, most of the patients had risk factors, such as advanced age, contralateral lung metastasis, use of nivolumab and so on [3,5,15,[27][28][29][30][31][32][33][34][35][36][37][38]. The patient we reported was an elderly woman with contralateral lung metastasis, PS was grade 2, and she developed grade 3 ILD with acute lung injury after 3 months of treatment with osimertinib.…”

“…After the remission of OsiILD with acute lung injury, it is necessary to choose appropriate drugs to control tumor progression and prolong the survival time of patients. Most of the reported cases of rechallenge of EGFR-TKI after OsiILD were treated with osimertinib [ 27 , 30 , 33 – 35 , 38 ], and a few patients without T790M mutation used first- or second-generation EGFR-TKI, such as gefitinib [ 36 ] and afatinib [ 15 , 37 ], all of which successfully controlled the tumor progression. Moreover, in the cases of using osimertinib, one part used the regular dose (80 mg per day) [ 26 , 34 , 35 ], and the other part reduced the dose (40 mg per day or 80 mg every other day) [ 27 , 30 , 33 , 38 ], which all achieved good therapeutic effect.…”

“…Most of the reported cases of rechallenge of EGFR-TKI after OsiILD were treated with osimertinib [ 27 , 30 , 33 – 35 , 38 ], and a few patients without T790M mutation used first- or second-generation EGFR-TKI, such as gefitinib [ 36 ] and afatinib [ 15 , 37 ], all of which successfully controlled the tumor progression. Moreover, in the cases of using osimertinib, one part used the regular dose (80 mg per day) [ 26 , 34 , 35 ], and the other part reduced the dose (40 mg per day or 80 mg every other day) [ 27 , 30 , 33 , 38 ], which all achieved good therapeutic effect. However, for the occurrence of OsiILD during the early use of osimertinib, it is obvious that there is a great risk of worsening the disease by choosing the routine or reduced dose of osimertinib to continue application.…”

“…According to current research, OsiILD may be primarily associated with a history or complication of ILD and previous treatment with programmed cell death protein-1 (PD-1) inhibitors such as nivolumab [22,26]. In several cases about OsiILD reported so far, most of the patients had risk factors, such as advanced age, contralateral lung metastasis, use of nivolumab and so on [3,5,15,27–38]. The patient we reported was an elderly woman with contralateral lung metastasis, PS was grade 2, and she developed grade 3 ILD with acute lung injury after 3 months of treatment with osimertinib.…”