Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study

Okada, Naoto; Kawazoe, Hitoshi; Takechi, Kenshi; Matsudate, Yoshihiro; Utsunomiya, Ryo; Zamami, Yoshito; Goda, Mitsuhiro; Imanishi, Masaki; Chuma, Masayuki; Hidaka, Noriaki; Sayama, Koji; Kubo, Yoshiaki; Tanaka, Akihiro; Ishizawa, Keisuke

doi:10.1016/j.clinthera.2018.11.004

Cited by 89 publications

(72 citation statements)

References 29 publications

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“…Several studies including patients treated with nivolumab for melanoma reported that the antitumor response was stronger in those exhibiting irAE. [20][21][22] To our knowledge, however, similar findings have not yet been reported in patients with MM who exhibit worse response to nivolumab compared with those with cutaneous melanoma. 23,24 Therefore, we conducted a single-center retrospective study of patients with unresectable or metastatic MM who were treated with nivolumab monotherapy with the aim to investigate whether the development of irAE was associated with clinical efficacy in these patients.…”

Section: Introductionsupporting

confidence: 65%

“…The results of these studies were consistent with the hypothesis that irAE are associated with a better outcome after this therapy. Several studies including patients treated with nivolumab for melanoma reported that the antitumor response was stronger in those exhibiting irAE . To our knowledge, however, similar findings have not yet been reported in patients with MM who exhibit worse response to nivolumab compared with those with cutaneous melanoma …”

Section: Introductionsupporting

confidence: 64%

“…[15][16][17][18][19] Similar findings based on retrospective analyses have also been reported in patients with melanoma treated with nivolumab. [20][21][22] However, the majority of the patients in these studies had cutaneous melanoma. In the current study including patients with advanced MM, the DCR was significantly higher in patients with than without irAE, while the ORR failed to demonstrate significant difference.…”

Section: Discussionmentioning

confidence: 92%

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Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

Otsuka

Sugihara

Mori

et al. 2020

The Journal of Dermatology

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Immune‐related adverse events (irAE) were reported to be associated with better outcomes in various cancers treated with the immune checkpoint inhibitor nivolumab. Considering that their development depends on host immune activation, irAE may reflect antitumor response in mucosal melanoma (MM). This single‐center retrospective study including patients with advanced MM receiving nivolumab monotherapy between August 2014 and September 2018 investigated whether the development of irAE was associated with clinical efficacy. The study patients were divided into those with and without irAE, and treatment efficacy and safety were evaluated. The study cohort of 27 patients included 20 (74%), six (22%) and one (4%) patient with primary MM in the head and neck, genitourinary and anorectal regions, respectively. The irAE onset was not significantly associated with the objective response rate in patients while it was significantly associated with the disease control rate. The median progression‐free survival in patients with and without irAE was 301 and 63 days, respectively. The median overall survival (OS) in patients with and without irAE was 723 and 199 days, respectively. According to the timing of irAE onset, the OS was better in seven patients who developed irAE after 180 days than in nine patients who developed irAE within 180 days. Although 16 patients (59%) experienced any grade irAE, including three (11%) with grade 3 or more irAE, there were no treatment‐related deaths. These results indicated that the development of irAE may correlate with improved survival in patients with MM treated with nivolumab monotherapy. Further studies are necessary to confirm these findings.

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Section: Introductionsupporting

confidence: 65%

Section: Introductionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

Otsuka

Sugihara

Mori

et al. 2020

The Journal of Dermatology

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“…A pooled analysis of safety data of nivolumab obtained from four prospective clinical trials in patients with advanced MM (n=576) showed a significantly higher ORR in patients with irAEs of any grade (48.6 vs. 17.8%, p<0.0001) (25). Similarly, in a small retrospective study including patients with advanced MM treated with nivolumab (n=15), Okada et al reported a higher disease control rate (DCR) (75% vs. 14%, p<0.05) and longer OS (p<0.05) in patients with any irAE compared to those without (26). A retrospective study focusing on the role of irAEs in patients with resected and unresectable MM (n=148) treated with nivolumab was conducted by Freeman-Keller et al (27).…”

Section: Iraes and Outcome In MMmentioning

confidence: 86%

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

et al. 2020

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“…In previous studies, irAEs have been defined as AEs with a potential immunologic cause and with necessity of frequent monitoring, or immunosuppressive and/or endocrine therapy according to the severity of the respective AE [6,[14][15][16]. Recently, several studies have shown that irAEs were associated with efficacy of anti-PD-1 antibody treatment in patients with melanoma and non-small cell lung cancer [17][18][19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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BackgroundRecent 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. In this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab.MethodsThe subjects of this study were AGC patients 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.ResultsOf 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 number of metastatic sites ≥2 (HR = 2.15; 95% CI, 1.02 to 4.54), high ALP level (HR = 2.50; 95% CI, 1.27 to 4.54), and absence of irAEs (HR = 9.54, 95% CI, 3.34 to 27.30 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), aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). There were no grade 4 or 5 adverse events related to nivolumab.ConclusionsDevelopment of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

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Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study

Cited by 89 publications

References 29 publications

Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

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

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