Refractory Severe Esophagitis During Durvalumab Therapy in a Patient With Locally Advanced NSCLC
Authors: Takahiro Utsumi, Kazuya Tsubouchi, Taishi Harada
Journal: Journal of Thoracic Oncology (2019)

Durvalumab, a class of chemotherapy known as immune checkpoint inhibitors, has shown significant efficacy in progression-free survival and overall survival among patients with stage III, locally advanced NSCLC.1Antonia S.J. Villegas A. Daniel D. et al.Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer.N Engl J Med. 2017; 377: 1919-1929Crossref PubMed Scopus (2464) Google Scholar, 2Antonia S.J. Villegas A. Daniel D. et al.Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC.N Engl J Med. 2018; 25https://doi.org/10.1056/NEJMoa1809697Google Scholar Esophageal immune-related adverse events (irAEs) have rarely been reported. We herein describe a case of refractory severe esophagitis during durvalumab therapy showing a marked response with systemic corticosteroid therapy. A 71-year-old man presented with hemoptysis. Stage III (cT3N2M0) NSCLC with left hilum and paratracheal lymph node metastasis was diagnosed (Fig. 1A, B). He received weekly carboplatin (area under the curve [AUC]: 2) and paclitaxel (40 mg/m2) with concurrent curative radiation therapy (66 Gy) (Fig. 1C). Radiation-induced esophagitis developed on the day 36 of the chemoradiotherapy course. After chemoradiotherapy, computed tomography (CT) revealed a remarkable reduction of lung tumor and lymph node metastasis, and biweekly durvalumab was intravenously administered. However, 28 days after the start of durvalumab, he complained of grade 3 dysphagia. Chest CT showed circumferential esophageal wall thickening, and esophagogastroduodenoscopy (EGD) revealed thick mucosal edema and esophageal stricture, suggesting the acute phase of radiation esophagitis (Fig. 2). Although endoscopic dilation was performed three times, esophageal stricture relapsed several days after each dilation. Because acute radiation esophagitis was prolonged and was refractory to standard therapy, we suspected that this symptom was an adverse event related to the durvalumab therapy. According to the treatment of colitis by checkpoint inhibitors, systemic corticosteroid therapy (prednisolone 30 mg daily) was started. His dysphagia markedly ameliorated after the prednisolone therapy and chest CT and EGD findings also dramatically improved (Fig. 3).Figure 2Circumferential esophageal wall thickening on chest computed tomography and thick mucosal edema and esophageal stricture on esophagogastroduodenoscopy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Chest computed tomography scan and esophagogastroduodenoscopy showing improvement of esophagitis after systemic corticosteroid therapy.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Radiation esophagitis is a common toxicity of thoracic radiation therapy especially when combined with chemotherapy. A previous meta-analysis has shown that the incidence of severe esophagitis with standard radiation therapy and concurrent chemotherapy was 18%.3Aupérin A. Le Péchoux C. Rolland E. et al.Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non–small-cell lung cancer.J Clin Oncol. 2010; 28: 2181-2190Crossref PubMed Scopus (1324) Google Scholar However, severe esophagitis can be controlled with standard management. Furthermore, a recent study of 79 patients showed the rates of grade 2 and grade 3 esophagitis to be 8% (n = 6) and 1.2% (n = 1), respectively, among those who received thoracic radiation therapy and immune checkpoint inhibitors.4von Reibnitz D. Chaft J.E. Wu A.J. et al.Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition.Adv Radiat Oncol. 2018; 3: 391-398Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Radiation esophagitis can be classified as acute or late esophagitis. The symptoms of acute radiation esophagitis typically peak after radiation therapy, and management including acid suppression, analgesics, and endoscopic dilation is generally effective. In our case, the EGD finding was not fibrosis but mucosal edema suggesting an acute reaction. The symptom of acute esophagitis atypically continued for approximately 1.5 months after the completion of radiation therapy, and was refractory to standard treatment, and corticosteroid therapy was drastically effective. Although corticosteroid therapy is uncommon for radiation-induced esophagitis, a previous case report had shown that esophagitis due to nivolumab was remarkably improved with systemic corticosteroid treatment; this is consistent with results seen in our patient.5Boike J. Dejulio T. Severe esophagitis and gastritis from nivolumab therapy.ACG Case Rep J. 2017; 4: e57Crossref PubMed Google Scholar These findings suggested esophagitis in our case was an irAE of durvalumab. To our knowledge, this is the first case report that shows durvalumab-induced refractory severe esophagitis. This case suggests that severe esophagitis during durvalumab therapy which is refractory to standard therapy should be treated as an irAE with systemic corticosteroids.