Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab.

Abstract

4049 Background: Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. Therefore, in this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab. Methods: The subjects of this study were AGC patients that had received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups. Results: Of the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3–407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p < 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p < 0.001). Multivariate analysis demonstrated that high ALP level (HR = 2.88; 95% CI, 1.51 to 5.51) and absence of irAEs (HR = 3.06, 95% CI, 3.06 to 23.46 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), increased aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). One of the 14 patients experienced the irAE after discontinuation of nivolumab due to progression of disease. There were no grade 4 or 5 adverse events related to nivolumab. Conclusions: Development of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

Recurrent gastric cancer sustaining a partial response after the nivolumab discontinuation because of immune-related adverse events: a case report

“…Besides, severe immune-related adverse events (irAE) are a crucial issue in the clinical management of patients with gastric cancer who undergo nivolumab chemotherapy [10]. A recent study reported a correlation between the presence or absence of irAE and the clinical bene t for nivolumab-treated patients with gastric cancer [11]. Here, we report a long-term survivor of recurrent gastric cancer maintaining a partial response (PR) after the nivolumab discontinuation because of irAE.…”

“…Some recent studies have paid attention to the predictive markers for tumor response to nivolumab in patients with gastric cancer [11,[16][17][18]. In addition, several studies have proposed the neutrophil-tolymphocyte ratio, Eastern Cooperative Oncology Group Performance Status, PD-L1 status, and mismatch repair as potential markers for predicting tumor response to nivolumab [16][17][18].…”

Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody.

“…In addition, similar results were obtained for OS and PFS. Masuda et al 12 ., who examined patients with gastric cancer, reported that PFS was extended by ICI therapy, which is consistent with our study. According to the waterfall plot showing tumour regression rates, all patients with a high rate had developed irAEs.…”

Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: PRO

“…Interestingly, in patients receiving CPIs, objective response rate, overall survival, and time to treatment failure do not seem to be negatively affected by the development of IRAEs (11,12). Moreover, there is limited data suggesting that outcomes are improved in patients experiencing IRAEs, irrespective of whether CPIs are reinitated (13)(14)(15)(16). Whether this also holds true for patients experiencing kidney IRAEs needs to be established.…”