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Dear Editor: We have already reported a case of a 38-year-old woman with advanced non-small cell lung cancer harboring a sensitive epidermal growth factor receptor (EGFR) L858R mutation with T790 M who was treated with osimertinib, a third generation EGFR-tyrosine kinase inhibitor (EGFR-TKI), which induced interstitial lung disease (ILD) after treatment with nivolumab [1]. In that report, we mentioned that an antiprogrammed cell death-1 (anti-PD1) antibody therapies may be a risk factor for EGFR-TKI-induced ILD. Herein, we describe the clinical course of a patient who was successfully treated with osimertinib rechallenge after osimertinib-induced ILD following treatment with nivolumab. In our patient, osimertinib-induced ILD improved within 2months after discontinuing osimertinib. She was treated with a combination of docetaxel and ramucirumab (10mg/kg, up to four cycles), as sixth-line chemotherapy, from August 2016, and then she received gemcitabine monotherapy (up to two cycles). However, no significant response was observed in any conventional chemotherapy, and tumor-related pain became worsen regardless of the administration of oxycodone. Therefore, osimertinib rechallenge was considered based on the expected clinical benefit of its antitumor efficacy over the risk of osimertinib-induced ILD recurrence. Although the risk of drug-induced ILD recurrence may be increased by rechallenge, we considered that the interaction between EGFR-TKI and the anti-PD1 antibody was decreased, because the interval from treatment with nivolumab had been more than 6 month. After obtaining informed consent, a rechallenge of osimertinib (80 mg, once daily) was started as eighth-line treatment for 8 months after the last initiation of nivolumab. One week after the re-administration of osimertinib concurrently without a steroid, her symptom (right chest pain) improved, and right tumor shadows were shrinking, as indicated by the chest radiograph (Fig. 1a, b). Furthermore, 3 months after treatment with osimertinib, the chest computed tomography scan showed a remarkable antitumor response with improvement in right pleural thickening without evidence of the recurrence of osimertinib-induced ILD (e.g., bilateral diffuse, faint, ground-glass opacities or consolidation) (Fig. 1c, d). Now, she continues to receive treatment with osimertinib. To our knowledge, this is the first case report of a successful osimertinib rechallenge following osimertinib-induced ILD after treatment with nivolumab. The strategy for treating lung cancer harboring a sensitive EGFR mutation is preferentially to administer EGFR-TKI. However, most patients unfortunately acquire resistance to EGFR-TKI. Several conventional chemotherapies or anti-PD1 therapies, in general, are initiated after resistance without a T790Mmutation to the first or second generation EGFR-TKI or the acquisition of osimertinib-resistance. In particular, PD1 antibody therapies are expecting to be one of the potential salvage chemotherapies. Kotake et al. reported a high frequency of osimertinibinduced ILD after immediate prior treatment with nivolumab in a series of 19 patients with EGFR-T790 M mutationpositive advanced non-small cell lung cancer who acquired resistance with the T790 M mutation [2]. They also showed * Hirotsugu Kenmotsu h.kenmotsu@scchr.jp

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Successful osimertinib rechallenge in a patient with advanced non-small cell lung cancer following osimertinib-induced interstitial lung disease after treatment with nivolumab