Hyperprogressive Disease in the Irradiation Field after a Single Dose of Nivolumab for Gastric Cancer: A Case Report

Abstract

Following the ATTRACTION-2 study, nivolumab was approved for advanced gastric cancer in Japan. However, pseudoprogression and hyperprogressive disease have been reported in patients treated with immune checkpoint inhibitors. We report a patient with gastric cancer who received nivolumab after radiotherapy only to experience rapid progression within the irradiation field after the first immunotherapy session. A 66-year-old man with dysphagia visited our hospital and was diagnosed with stage IV gastroesophageal cancer (human epidermal growth factor receptor-2 score = 0). He commenced a G-SOX regimen (S-1 80 mg/m² on days 1–14 and oxaliplatin 100 mg/m² on day 1, repeated every 3 weeks) in June 2017. The dysphagia worsened despite 3 cycles of G-SOX, and computed tomography (CT) revealed constriction of the gastroesophageal junction. To ameliorate the dysphagia, palliative chemoradiotherapy (S-1 and 50.4 Gy in 28 fractions) was performed starting in August 2017. The patient’s dysphagia had not resolved after completing radiotherapy, and pain on swallowing worsened. Nivolumab (3 mg/m² every 2 weeks) was administered 7 days after the completion of radiotherapy. The patient experienced malaise and worsening dysphagia before the second cycle. CT 15 days after the first nivolumab administration revealed rapid progression in the irradiation field. His general condition rapidly deteriorated, and he died 24 days after the first administration. This episode suggests that administration of nivolumab after radiotherapy may be a risk factor for hyperprogressive disease.

Hyperprogression in PDL1 Expressive, Recurrent Gastroesophageal-junction Adenocarcinoma After Pembrolizumab

“…Hyperprogression has so far been increasing described in a wide variety of cancers including lung cancers, head and neck cancers urothelial carcinoma, and melanomas [14-16]. While hyperprogression has been previously documented in GEJ tumors after nivolumab, to our knowledge there has not been reportage of HP in GEJ tumors after usage of pembrolizumab as we have described in our case [1].…”

“…Even though hyperprogression is increasingly reported among other cancers, it is exceedingly rare among gastroesophageal junction (GEJ) tumors. The previously reported case in a GEJ tumor was in the setting of nivolumab use [1]. To our knowledge there has been no previously reported hyperprogression in GEJ tumors after pembrolizumab use and we present the first known occurrence of this in the case below.…”

Neutrophil-to-lymphocyte ratio as a predictive or prognostic factor for gastric cancer treated with nivolumab: a multicenter retrospective study

“…However, the activities of immune checkpoint inhibitors (ICIs), are different from cytotoxic agents, and pseudoprogression and hyperprogressive disease have been reported in patients treated with ICIs. In gastric cancer, hyperprogressive disease has been previously reported [ 10 ]. When the pseudoprogression occurred, we considered a change in treatment according to RECIST because we could not decide whether the progression was pseudoprogression or hyperprogressive disease.…”

Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report

“…The literature regarding therapeutic options for hyperprogression of patients is limited to case reports, although data regarding second progression‐free survival from randomized trials may shed more light on this question in the future. In some case reports, patients rapidly declined and died without any subsequent therapy . A case report detailing post‐pembrolizumab hyperprogression in an anorectal melanoma patient reported that the patient received one cycle of dacarbazine without clinical improvement .…”

“…In some case reports, patients rapidly declined and died without any subsequent therapy. 11,12 A case report detailing post-pembrolizumab hyperprogression in an anorectal melanoma patient reported that the patient received one cycle of dacarbazine without clinical improvement. 13 In fact, most of the studies thus far recommend avoiding future immunotherapy use altogether in this subgroup given the risks of hyperprogression.…”