Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab

Toi, Yukihiro; Sugawara, Shunichi; Kawashima, Yosuke; Aiba, Tomoiki; Kawana, Sachiko; Saito, Ryoichi; Tsurumi, Kyoji; Suzuki, K.; Shimizu, Hisashi; Sugisaka, Jun; Ono, Hirotaka; Domeki, Yutaka; Terayama, Keisuke; Nakamura, Atsushi; Yamanda, Shinsuke; Kimura, Yuichiro; Honda, Yoshihiro

doi:10.1634/theoncologist.2017-0384

Cited by 218 publications

(216 citation statements)

References 34 publications

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“…On the other hand, the differences in survival rates between the subgroups seem to us so impressive that with a bigger sample size, statistically significant differences would emerge. Interestingly, our finding of a higher incidence of irAEs of any grade in patients with non‐low SMM is consistent with recent reports that described significant associations between irAEs and a greater benefit with anti‐PD‐1/PD‐L1 treatments …”

Section: Discussionsupporting

confidence: 92%

“…Interestingly, our finding of a higher incidence of irAEs of any grade in patients with non-low SMM is consistent with recent reports that described significant associations between irAEs and a greater benefit with anti-PD-1/PD-L1 treatments. 8,9 We cannot make any definitive conclusions, but only some speculative reflections on how nutritional status and body composition could affect the immune response and clinical outcomes of ICI treatments. Some authors have already speculated about the negative influence that alterations in body composition of sarcopenic patients could have on declining immunity.…”

Section: Discussionmentioning

confidence: 99%

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Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

et al. 2019

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Sarcopenia represents one of the hallmarks of all chronic disease, including non‐small cell lung cancer (NSCLC). A computed tomography scan is an easy modality to estimate the skeletal muscle mass through cross‐sectional image analysis at the level of the third lumbar vertebra (L3). Baseline skeletal muscle mass (SMM) was evaluated using gender‐specific cutoffs for skeletal muscle index in NSCLC patients administered immunotherapy with nivolumab to evaluate its possible correlations with clinical outcomes. From April 2015 to August 2018, 23 stage IV NSCLC patients were eligible for image analysis. Nine patients (39.1%) had low SMM. Among patients with baseline low and non‐low SMM, median progression free survival was 3.1 and 3.8 months, respectively (P = 0.0560), while median overall survival was 4.1 and 13 months, respectively (P = 0.2866). This hypothesis‐generating preliminary report offers the opportunity to speculate about the negative influence of sarcopenia on immune response. In our opinion, nutritional status could affect the clinical outcomes of immunotherapy, even if we cannot make definitive conclusions here. Further studies on the topic are required.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

et al. 2019

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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%

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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“…Recently, several studies have reported a positive correlation between irAEs and improved clinical outcomes . However, an association between ILD and the efficacy of ICIs has not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5] Recently, several studies have reported a positive correlation between irAEs and improved clinical outcomes. 6,7 However, an association between ILD and the efficacy of ICIs has not been fully investigated. The aim of this study was to evaluate the relationship between the development of ILD and clinical efficacy and to clarify the features and risk factors of ILD for patients with advanced NSCLC treated with ICIs.…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

et al. 2020

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Background Interstitial lung disease (ILD) induced by immune checkpoint inhibitors (ICIs) is a potentially life‐threatening adverse event. The purpose of this study was to evaluate whether the development of immune‐related adverse events (irAEs), especially ILD, was associated with treatment efficacy and to research the features and risk factors of ILD in advanced non‐small cell lung cancer (NSCLC). Methods Between December 2015 and November 2018, 130 advanced NSCLC patients were treated with nivolumab, pembrolizumab or atezolizumab. The patients were categorized into two groups (irAEs group or non‐irAEs group). Subsequently, we divided the irAEs group into two groups based on the incidence of ILD (ILD group and irAEs‐non‐ILD group). Treatment efficacy and the characteristics of ILD were evaluated. Results A total of 39 (30%) patients developed irAEs. ILD was observed in 16 (12%) patients. Patients with ILD had a higher objective response rate (ORR) compared with irAEs‐non‐ILD patients and non‐irAEs patients (63%, 43% and 22%, respectively). Median progression‐free survival (mPFS) was 15.9 months in ILD patients, 5.4 months in irAEs‐non‐ILD patients and 3.3 months in non‐irAEs patients (log‐rank test, P = 0.033). Pre‐existing interstitial pneumonia (IP) was an independent risk factor for ILD‐induced ICIs (odds ratio [OR] 14.7; 95% confidence interval [CI]: 2.16–99.6, P = 0.006). Conclusions ORR and PFS were significantly better in ILD patients than in irAEs‐non‐ILD and non‐irAEs patients. Pre‐existing history of IP was an independent risk factor for ILD‐induced ICIs.

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Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab

Cited by 218 publications

References 34 publications

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

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 checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

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