期刊
CANCER TREATMENT REVIEWS
卷 92, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ctrv.2020.102134
关键词
Immunotherapy; Immune-related adverse events; Checkpoint inhibitors; Efficacy; Nivolumab; Pembrolizumab; Ipilimumab; Toxicity; Melanoma; Non-small cell lung cancer
类别
资金
- London Regional Cancer Program's Catalyst Grant Program
- Keith Smitt Translational Research Grants
The study showed a positive correlation between the occurrence of immune-related adverse events and treatment efficacy (ORR, PFS, OS) in patients treated with immune checkpoint inhibitors for various solid malignancies. However, grade 3 or 4 adverse events resulted in better objective response rate but worse overall survival.
Background: The use of immune checkpoint inhibitors (ICIs) has become standard therapy in many tumor sites. The aim of this study is to systematically review the literature to determine whether the incidence of immunerelated adverse events (irAEs) after the use of ICIs is associated with clinical outcomes in all solid malignancies. Methods: Embase and PubMed were searched from January 1st, 2000 until March 14, 2020 for relevant studies assessing the relationship between irAEs and treatment efficacy. Outcome measures of interest included: incidence of irAEs, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: Of 3384 unique citations, 51 studies met inclusion criteria. Studies included melanoma (n = 21), lung (n = 19), renal (n = 4), urothelial (n = 1), head and neck (n = 2) and gastrointestinal cancers (n = 1). In patients with metastatic melanoma (n = 1474), the development of irAEs (irAE + versus irAE-) was associated with better weighted average OS (15.24 months (95% CI 9.95 to 20.5) versus 8.94 months (95% CI 7.76 to 10.1), HR = 0.46 (n = 640, CI 0.35-0.62, p < 0.00001), PFS (17.61 months (95% CI 10.1 to 25.1) versus 2.23 months (95% CI 1.77 to 2.68), HR = 0.51 (n = 1763, CI 0.42-0.63, p < 0.00001), and ORR (37.67% (95% CI 32.8 to 42.5) versus. 23.44% (95% CI 17.8 to 29.1). Similarly, in lung cancer patients, the ORR (irAE + versus. irAE-) was 41.49% (95% CI 36.5 to 46.5) versus 18.01% (95% CI 13.5 to 22.6). The weighted average PFS and OS were 8.97 months (95% CI 7.14 to 10.8) versus 3.06 months (95% CI 2.4 to 3.72) with HR = 0.46 (n = 1575, CI 0.39-0.54, p < 0.00001) and 19.07 months (95% CI 14.3 to 23.8) versus 7.45 months (95% CI 5.34 to 9.56) HR = 0.40 (n = 1085, CI 0.30-0.51, p < 0.00001), respectively. Improved treatment efficacy in patients who developed irAEs was also seen in renal cell carcinoma, urothelial and head and neck cancers. Notably, grade 3 or 4 irAEs were associated with increased ORR but worse OS. Conclusion: A positive association was noted between the development of irAEs and ORR, PFS, and OS in patients treated with ICIs, irrespective of disease site, type of ICI and irAE. Grade 3 or higher toxicities resulted in better ORR, but worse OS.
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