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

Abstract

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.

Osimertinib-Induced Unilateral Diffuse Alveolar Hemorrhage in a Patient With Pulmonary Adenocarcinoma

“…This was a rare case of osimertinib-induced DAH. To our knowledge, there were only two osimertinib-induced and four other EGFR-TKI-induced DAH cases ( Table 1 ) [ 1 , 4 - 8 ]. We could not find a report of DAH induced by other EGFR-TKIs; afatinib and dacomitinib, and anti-EGFR antibodies; cetuximab and panitumumab.…”

“…Compared with the previous cases of EGFR-TKI-induced DAH, our case was interesting in distribution of DAH shadow, i.e., unilaterally localized consolidations. A 65-year-old US woman required intubated mechanical ventilation and then improved by steroid pulse therapy [ 1 ]. Her CT images were similar to our case in that the diffuse consolidation did not bilaterally spread, but was localized in the left upper lobe.…”

“…Therefore, osimertinib has become a standard drug as the first-line treatment for these patients. Owing to highly selective inhibition of mutated EGFR and lower activity against wild-type EGFR , less than 5% of patients develop significant pulmonary toxicity [ 1 ]. Digestive and dermatological symptoms are representative as adverse effects of osimertinib.…”

“…EGFR-TKI is a rare drug that causes DAH. As pulmonary adverse effects of osimertinib, acute pneumonitis, eosinophilic pneumonia and fleeting asymptomatic infiltrates on imaging have been reported [ 1 ].…”

Successful Rechallenge with Osimertinib after Very Acute Onset of Drug-Induced Pneumonitis

“…Osimertinib is the treatment of choice for patients with NSCLC with acquired T790M resistance, and first-line treatment in patients with exon 21 L858R and exon 19 mutations [5]. It has also been linked to a wide range of pulmonary complications ranging from asymptomatic opacities/infiltrates on imaging called TAPO [4] to catastrophic diffuse alveolar hemorrhage [6]. DI-ILD has been associated with EGFR-TKI therapies, including osimertinib in 1-3% of patients with reported mortality in up to 22% of the patients [7].…”