Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis

Ricciuti, Biagio; Genova, Carlo; Giglio, Andrea De; Bassanelli, Maria; Bello, Maria Giovanna Dal; Metro, Giulio; Brambilla, Marta; Baglivo, Sara; Grossi, Francesco; Chiari, Rita

doi:10.1007/s00432-018-2805-3

Cited by 291 publications

(256 citation statements)

References 11 publications

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“…Immune‐related adverse events were not associated with better OS in patients with metastatic NSCLC. In concordance with our findings, several retrospective analyses have reported improved PFS and OS in patients with advanced NSCLC or melanoma that developed grade 2 or higher irAEs . A prospective cohort of 43 patients with NSCLC treated with nivolumab demonstrated a higher objective response rate in the patients that experienced irAEs (37%) compared with those without irAEs (17%), as well as longer median PFS (6.4 vs. 1.5 months) .…”

Section: Discussionsupporting

confidence: 91%

“…Several studies have described a correlation between hyper‐immunity and response to therapy, , and like in our study, irAEs were associated with improved PFS for both cohorts and better OS in the melanoma cohort. Owen et al reported that sex was not associated with an increased risk for irAEs, but this analysis was in an older population with a median age of 67 years.…”

Section: Discussionsupporting

confidence: 84%

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Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

et al. 2019

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Background Immune‐related adverse events (irAEs) have emerged as a serious clinical issue in the use of immune checkpoint inhibitors (ICIs). Risk factors for irAEs remain controversial. Therefore, we studied sex differences in irAEs in patients treated with anti‐programmed cell death protein 1 (PD‐1) therapy. Materials and Methods All patients with metastatic melanoma and non‐small cell lung cancer (NSCLC) treated with anti‐PD‐1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Kaplan‐Meier method and log‐rank test was used for time‐to‐event analysis. Results In 245 patients with metastatic melanoma, premenopausal women were more likely to experience irAEs (all grades) compared with postmenopausal women and men (67% vs. 60% vs. 46%), primarily because of an increase in endocrinopathies (33% vs. 12% vs. 10%, respectively). In patients with NSCLC (231 patients), women (all ages) were also more likely to develop irAEs of all grades (48% vs. 31%). Women with NSCLC were more likely to develop pneumonitis (11% vs. 4%) and endocrinopathies (14% vs. 5%). No differences in grade ≥3 toxicities were seen across sexes in both cohorts, but women were more likely to receive systemic steroids for the treatment of irAEs compared with men. Better progression‐free‐survival was observed in women with NSCLC and irAEs (10 months vs. 3.3 months) compared with women without irAEs. Conclusion Women with metastatic melanoma and NSCLC are more likely to experience irAEs compared with men. We also observed differences between sexes in the frequency of certain irAEs. Larger studies are needed to investigate the mechanisms underlying these associations. Implications for Practice The results of this study suggest that women may be at a higher risk for immune‐related adverse events (irAEs) compared with men when treated with anti‐programmed cell death protein 1 therapy. In addition, women were more likely to develop certain irAEs, including endocrinopathies and pneumonitis. Close follow‐up of women undergoing treatment with immune checkpoint inhibitors will allow clinicians to diagnose these treatment‐related complications early, potentially reducing their associated morbidity and mortality. In addition, a possible association between irAEs and response to therapy was observed.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 84%

Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

et al. 2019

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“…Several studies have shown that the development of irAE is associated with improved survival after nivolumab monotherapy in patients with non-small-cell lung cancer. [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.…”

Section: Discussionsupporting

confidence: 75%

“…To that end, several studies were conducted in patients with non-small-cell lung cancer treated with nivolumab to determine whether patients with irAE may derive a greater clinical benefit. [15][16][17][18][19] 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.…”

Section: Introductionsupporting

confidence: 84%

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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“…The study conducted by Ricciuti et al, including patients with advanced NSCLC treated with nivolumab (n=195), showed significantly higher ORR (43.5% vs. 10.0%, p<0.0001) and DCR (70.5% vs. 18.1%, p<0.0001), as well as longer PFS and OS (HR=0.41, p<0.0001 and HR=0.33, p<0.0001) in patients with irAEs compared with patients without any (36). The results of the Cox multivariate model showed the following factors to be significant for PFS: any irAE (HR=0.48, p<0.0001), pulmonary (HR=0.56, p=0.038), gastrointestinal (HR=0.055, p=0.021), endocrine (HR=0.59, p=0.011) and skin irAEs (HR=0.57, p=0.031); significant factors for OS were: any irAE (HR=0.38, p<0.0001), pulmonary (HR=0.46, p=0.022), gastrointestinal (HR=0.50, p=0.045), endocrine (HR=0.45, p=0.001) and skin irAEs (HR=0.80, p=0.043) (36). A 6weeks landmark analysis showed a significant association of irAEs with OS (HR=0.55, p=0.021) and a 12-weeks landmark analysis showed an even deeper and statistically significant association with PFS (HR=0.48, p<0.0001) and OS (HR=0.40, p<0.0001) (36).…”

Section: Iraes and Outcome In Nsclcmentioning

confidence: 98%

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

et al. 2020

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Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis

Cited by 291 publications

References 11 publications

Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

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

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