Abstract. Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. Following nivolumab as a sixth-line treatment, an EGFR-T790M-encoding mutation in EGFR exon 20 was identified by re-biopsy. Osimertinib was therefore initiated as a seventh-line treatment. A partial response was subsequently noted; however, 63 days after initiation of the treatment the patient presented with dyspnea with decreased oxygenation in the absence of fever and sputum. A computed tomography scan revealed the emergence of ground-glass opacities with bronchiectasis in both lungs, and a diagnosis of ILD due to osimertinib was made. Following steroid pulse therapy with discontinuation of osimertinib, the patient's chest findings and respiratory condition improved. Therefore, it is considered that anti-PD-1 therapies may be associated with a risk of ILD during subsequent osimertinib treatment.
IntroductionThe discovery of epidermal growth factor receptor (EGFR)-acti vating mutations in non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors (TKIs) have changed the strategy of NSCLC therapy. Recently, EGFR-TKIs, including gefitinib, erlotinib and afatinib, have become the standard therapy for patients with advanced EGFR-mutated NSCLC. However, the majority of the patients progress and second-line therapy is required.The EGFR T790M point mutation (T790M) is the most common mechanism underlying drug resistance to EGFR-TKIs in EGFR mutation-positive NSCLC patients. Osimertinib (AZD9291) is a third-generation EGFR-TKI approved for the treatment of EGFR-T790M-positive NSCLC (1). Furthermore, immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has also shown promise in changing the strategy of NSCLC therapy. Nivolumab, an anti-PD-1 inhibitor, is a novel drug used in the second-line treatment of NSCLC (2). In both EGFR-TKI and immune checkpoint inhibitors therapy, interstitial lung disease (ILD) is recognized as one of most severe adverse events. These two therapies may be sequentially applied in the same patient, but the effects of the interaction between these two drugs on the risk of ILD remains unclear. A case of ILD that occurred during osimertinib treatment in a patient with a history of previous nivolumab treatment is reported herein.
Case reportA 59-year-old female was diagnosed with stage IV (cT3N2M1a) lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. The patient was treated with platinum-pemetrexed with bevacizumab...