Osimertinib-Induced Interstitial Lung Disease Presenting as Eosinophilic Pneumonia

Tachi, Hiroaki; Shiozawa, Toshihiro; Sakai, Chio; Kasuga, Mariko; Nakazawa, Kensuke; Morishima, Yuko; Satoh, Hiroaki; Hizawa, Nobuyuki; Sakashita, Shingo; Sekine, Ikuo

doi:10.1016/j.jtho.2017.03.022

Cited by 13 publications

(15 citation statements)

References 5 publications

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“…Second, Wang et al reported that Osimertinib decreases G2/M phase arrest in irradiated cells, delaying DNA damage repair, which is considered a radiation-sensitizer; however, this effect also enhances radiation injury in normal lung tissue [11]. In addition, infiltration of lymphocytes and eosinophils has been reported in some Osimertinib-induced ILD, which is also a risk factor for radiation pneumonitis after radiotherapy [12,13]. This is the first study to report an especially high rate for grade 2 or worse RP in response to Osimertinib combined with simultaneous TRT, even though V5, V20 and MLD seem unlikely to induce RP.…”

Section: Discussionmentioning

confidence: 99%

An especially high rate of radiation pneumonitis observed in patients treated with thoracic radiotherapy and simultaneous osimertinib

Jia

Guo

Wang

et al. 2020

Radiotherapy and Oncology

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Section: Discussionmentioning

confidence: 99%

An especially high rate of radiation pneumonitis observed in patients treated with thoracic radiotherapy and simultaneous osimertinib

Jia

Guo

Wang

et al. 2020

Radiotherapy and Oncology

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“…ILD, including acute ILD, was a later complication at about 4 months of therapy in the previous case reports [3, 6]. The asymptomatic pulmonary opacities occurred at approximately 8-24 weeks of therapy [7, 8], whereas the eosinophilic pneumonia occurred at 2 weeks of therapy [9]. Some patients were also given steroids which seemed to be an effective adjunct to medication discontinuation in the improvement in respiratory symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…Osimertinib is usually well tolerated with less than 5% of patients developing toxicity from the medication, usually within the first few months. Previously reported pulmonary adverse reactions include pneumonitis including nonspecific interstitial pneumonia [3–6] or other acute interstitial processes [3, 6], fleeting asymptomatic infiltrates on imaging [7, 8], and eosinophilic pneumonia [9]. Previously reported pulmonary toxicities are summarized in Table 1.…”

Section: Discussionmentioning

confidence: 99%

Emerging Risk Profile of Lung Cancer Therapy: Diffuse Alveolar Hemorrhage from Osimertinib

Forte

Sangani

2019

Case Reports in Oncological Medicine

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Osimertinib is an oral epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used primarily in the treatment of metastatic non-small cell lung cancer. It is usually well tolerated with less than 5% of patients developing significant pulmonary toxicity from the medication, typically within the first few months after initiation. Previously reported pulmonary adverse reactions include pneumonitis (nonspecific interstitial pneumonia or other forms of acute interstitial process), fleeting asymptomatic infiltrates on imaging, and eosinophilic pneumonia. We present an interesting case of a 65-year-old female with recurrent metastatic adenocarcinoma of the lung, treated with Osimertinib for 4 months, who developed a previously unreported toxicity of diffuse alveolar hemorrhage (DAH) requiring mechanical ventilatory support.

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“…Although the incidence of osimertinibinduced ILD has been reported to be as high as 12-13% (26,27), the underpinning mechanism is still not entirely clear, and only a few related reports have been published. In a rare case report of osimertinib-induced ILD, the pathological manifestation was acute eosinophilic pneumonia (28). During CT examination, TKI-induced ILD can manifest as a single ground-glass opacity, multiple consolidations, scattered multiple ground-glass opacities with interlobular septal thickening, or extensive groundglass opacity lesions or consolidation areas in both lungs with tractive bronchiectasis (29).…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of EGFR T790M-mutant non-small cell lung cancer with almonertinib after osimertinib-induced interstitial lung disease: a case report and literature review

Zhong

et al. 2021

Ann Transl Med

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Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have revolutionized the standard treatment for EGFR T790M-positive non-small cell lung cancer (NSCLC). Osimertinib is one of the third-generation EGFR-TKIs and is currently the most advanced in clinical development. Interstitial lung disease (ILD) is a potentially fatal side effect of osimertinib use.Successful rechallenge with the second-generation TKI afatinib following osimertinib-induced ILD has been reported. However, few reports have discussed the safety and efficacy of third-generation TKI rechallenge in this patient population. In this paper, a case of lung adenocarcinoma is retrospectively analyzed, and the relevant literature is reviewed. The patient was initially diagnosed with early lung cancer, for which surgical treatment was performed. The postoperative diagnosis indicated stage IB (pT2N0M0) right lung adenocarcinoma. Genetic testing (amplification-refractory mutation system) revealed EGFR exon 19 deletion. More than 2 years after surgery, multiple metastases occurred in both lungs, so gefitinib (250 mg per day) was administered. However, 6 months after the start of gefitinib treatment, the tumor progressed.Lung tumor biopsy was performed for genetic testing (NGS) and an EGFR T790M mutation was observed.Subsequently, second-line treatment with osimertinib (80 mg per day) was given for 3 months. The evaluated response suggested a partial response (PR) with the occurrence of grade 3 ILD. Pemetrexed plus bevacizumab chemotherapy was subsequently administered, resulting in stable disease. However, following a severe drug reaction after six courses, the patient's chemotherapy was discontinued. Another thirdgeneration TKI, almonertinib (110 mg per day), was rechallenged based on no ILD having been reported in a phase I/II study of this drug. After 4 months of almonertinib administration and 6 months without ILD recurrence, partial remission was attained. This is the first report of successful treatment with almonertinib after osimertinib-induced ILD. The results suggested that almonertinib had a significant effect in patients with EGFR T790M mutation, with fewer side effects and better survival benefits for patients with advanced lung cancer.

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Osimertinib-Induced Interstitial Lung Disease Presenting as Eosinophilic Pneumonia

Cited by 13 publications

References 5 publications

An especially high rate of radiation pneumonitis observed in patients treated with thoracic radiotherapy and simultaneous osimertinib

An especially high rate of radiation pneumonitis observed in patients treated with thoracic radiotherapy and simultaneous osimertinib

Emerging Risk Profile of Lung Cancer Therapy: Diffuse Alveolar Hemorrhage from Osimertinib

Successful treatment of EGFR T790M-mutant non-small cell lung cancer with almonertinib after osimertinib-induced interstitial lung disease: a case report and literature review

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