Early Onset Immune-Related Adverse Event to Identify Pseudo-Progression in a Patient With Ovarian Cancer Treated With Nivolumab: A Case Report and Review of the Literature

Abstract

Background: Immune checkpoint inhibitors (ICIs) have shown clinical benefit in many advanced tumors, however, pseudo-progression is a noted phenomenon of ICIs characterized by radiologic enlargement of the tumor burden, followed by regression. How to differentiate pseudo-progression from progression remains a critical clinical issue. Recent studies have demonstrated the association between immune-related adverse events (irAEs) and efficacy of ICIs. Here we demonstrated an ovarian cancer patient treated with nivolumab in whom the early-onset irAE was identified to differentiate pseudo-progression from progression. Case presentation: Here we present the case of a 47-years-old woman with histopathologically confirmed diagnosis of metastatic ovarian cystadenocarcinoma. Immunohistochemical examination showed 10% of tumor cells to express the programmed cell death receptor ligand 1 (PD-L1) and a 381-gene panel sequencing in a College of American Pathologists (CAP) certificated lab revealed a moderate mutational tumor burden with 5.7 Mutants/Mb. The patient received nivolumab 100 mg every 2 weeks as a fourth line treatment. Within the first 2 months, the tumor volume increased by 23.6%. However, the patient experienced an elevation of Alanine aminotransferase (ALT) and Aspartate aminotransmerase (AST), which was diagnosed as the immune-related hepatitis. Thus, the treatment continued and afterwards, the patient reached a partial response (PR) to nivolumab and the progression-free survival was 9 months. Conclusion: To our knowledge, this is the first case describing early-onset immune-related adverse events to identify pseudo-progression in a patient with ovarian cancer treated with nivolumab, and PD-L1 expression level may be a predictive biomarker in the immunotherapy of ovarian cancer.

Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer

“…Pseudoprogression has been described in the literature in nivolumab-treated patients with ovarian cancer. 13 14 However, evidence is limited and some reports suggest that pseudoprogression with nivolumab may be less common than initially suspected, at least in some tumor types. 15 16 Long-term OS results from the present study may provide further insight.…”

Case Report: Pseudoprogression With Nivolumab and Bevacizumab Followed by Recurrent Immune-Related Pneumonitis in Urothelial Carcinoma With Lung Metastasis

“…Hui et al. had used early-onset irAEs as a predictor to differentiate pseudoprogression ( 10 ). Alternatively, as another sign of immune overactivation, pseudoprogression may also predict future irAEs.…”

“…According to previous studies, both irAEs and pseudoprogression could be regarded as evidence of rigorous immune activation that correlate with survival benefits. Hui et al had used early-onset irAEs as a predictor to differentiate pseudoprogression (10). Alternatively, as another sign of immune overactivation, pseudoprogression may also predict future irAEs.…”

Imaging assessment of toxicity related to immune checkpoint inhibitors

“…Interestingly, the occurrence of (low-grade) irAEs has been correlated with treatment efficacy and improved clinical outcomes as measured by overall response rate, progression-free survival and overall survival (6,17). Furthermore early-onset immune-related hepatitis as irAEs was used to detect pseudoprogression and to distinguish this response pattern from true progression in a case of metastatic ovarian cancer treated with nivolumab (138).…”