Analyse The Association Between Adverse Events (Aes) And Survival In Patients Treated With Immune Checkpoint Inhibitors (Icis)
ANNALS OF ONCOLOGY(2019)
Abstract
Background ICIs with a programmed death protein 1 (PD-1) or programmed death protein ligand 1 (PD-L1) antibodies have shown survival benefits for various metastatic cancer patients. However, some patients treated with ICIs may suffer from AEs. We investigated the association between AEs and survival in metastatic cancer patients treated with PD-1/PD-L1 inhibitors. Methods We retrospectively reviewed medical records of metastatic cancer patients treated with pembrolizumab, nivolumab or atezolizumab from April 2016 to June 2019 for AEs, progression-free survival (PFS), and overall survival (OS). Kaplan-Meier curve was used to estimate survival probability and the Cox proportional hazard model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) between each interesting group. Results We enrolled 101 patients. Primary cancers were urothelial carcinoma (n = 52), lung cancer (n = 42), hepatocellular carcinoma (n = 5), and cholangiocarcinoma (n = 2). Atezolizumab was the most common prescribed agents (n = 69), followed by pembrolizumab (n = 29) and nivolumab (n = 3). The AEs happened more frequently were associated with lung (n = 25), skin (n = 24), endocrine (n = 17), and liver (n = 11). Median time for these AEs happened was 1.4 months. Median OS (mOS) for these patients was 16.9 months and median PFS (mPFS) was 9.1 months. Among various AEs, patients with skin AE had significantly longer PFS and OS compared to those without skin AE (mPFS: 11.9 months vs. 4.9 months, p = 0.0016 ; mOS: 16.4 months vs. 10.3 months, p = 0.0022). In comparison with those without endocrine AE, the occurrence of endocrine AE was associated with an improved PFS (mPFS: 19.2 months vs. 6.0 months, p = 0.0476 ) and a trend toward to OS (mOS: 19.4 months vs. 10.9 months, p = 0.1731 ). There were no survival difference between patients who experienced lung or liver AEs. Conclusions In metastatic cancer patients treated with anti-PD-1/PD-L1 ICIs, development of skin or endocrine AEs may indicate improved survival time. The patients with AEs involved visceral organ, like lung or liver, have no better survival time. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
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Key words
immune checkpoint inhibitors,adverse events,icis
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