Real-world use and survival outcomes of immune checkpoint inhibitors in patients with non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14111-e14111
Author(s):  
Bora Youn ◽  
Nikolaos Trikalinos ◽  
Vincent Mor ◽  
Ira Wilson ◽  
Issa Dahabreh

e14111 Background: Little is known about the real-world use and survival outcomes of immune checkpoint inhibitors among elderly patients with non-small cell lung cancer (NSCLC). Methods: Using the SEER-Medicare data, we identified 1,338 patients who were diagnosed with pathologically confirmed stage 1-4 NSCLC between 2002 and 2015 and initiated nivolumab or pembrolizumab in 2016. We examined the association of patient and disease characteristics, and treatment history with overall survival, from initiation through December 31, 2017. We estimated survival curves using the Kaplan-Meier method and identified predictors of survival using multivariable Cox proportional hazards regression. Results: The median age at immune checkpoint inhibitor initiation was 74.8 years. The majority of patients were initially diagnosed with stage 4 disease (42.7%). Median time from diagnosis to initiation were 13.9 and 19.0 months for those initially diagnosed with stage 4 and 1-3 disease, respectively. Median overall survival was 9.5 months. In multivariable analyses, multiple comorbid conditions, squamous histology, history of non-platinum doublet systemic therapy, recent radiation therapy, and shorter time from initial diagnosis to initiation were statistically significantly associated with increased hazard of death (Table). Demographics, stage at initial diagnosis, and prior oral targeted therapy were not significantly associated with the hazard of death. Conclusions: Real-world data show that factors that are generally related to poor prognosis remain predictors of survival in elderly patients treated with immune checkpoint inhibitors.[Table: see text]

Cancer ◽  
2020 ◽  
Vol 126 (5) ◽  
pp. 978-985 ◽  
Author(s):  
Bora Youn ◽  
Nikolaos A. Trikalinos ◽  
Vincent Mor ◽  
Ira B. Wilson ◽  
Issa J. Dahabreh

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A840-A840
Author(s):  
Lindsey Shantzer ◽  
Sean Dougherty ◽  
Wendy Novicoff ◽  
John Melson ◽  
Daniel Reed ◽  
...  

BackgroundImmune checkpoint inhibitors (ICIs) have become the backbone of treatment for most driver-mutation negative, advanced non-small cell lung cancers. ICIs have been approved both as monotherapy and in combination with chemotherapy for front line management. While ICIs are generally regarded as well-tolerated, an unintended activation of the immune system can result in a variety of immune-related adverse events (irAEs), which can limit their use in severe cases. In patients with NSCLC treated with ICI monotherapy, the occurrence of an irAE and the development of multisystem irAEs have been associated with improved clinical outcomes, suggesting irAE occurrence could have prognostic implications.1–4 However, in patients treated with combination immunotherapy plus chemotherapy, the correlation between irAEs and survival has not been completely elucidated.MethodsWe conducted a retrospective chart review of 94 patients with advanced NSCLC treated with a combination of ICI plus chemotherapy between 2015 and 2021 to evaluate for a correlation between irAE occurrence and overall survival (OS). Patients were divided into two groups: those who experienced at least one irAE and those who did not experience an irAE. To account for immortal time bias, we conducted landmark analyses at 12 and 24 weeks. We additionally investigated the impact of multisystem irAEs on clinical outcomes and described the profile of irAEs observed at our institution.ResultsAmong the 94 evaluable patients identified in our population, 43.6% experienced at least one irAE. Of those patients who experienced an irAE, 26 (63.4%) experienced a single irAE, 9 (22.0%) experienced 2 irAEs, and 6 (14.6%) experienced 3 or more irAEs. The most commonly observed irAEs were dermatitis followed by pneumonitis and colitis. In our cohort, patients with at least one irAE had significantly longer median OS (16.8 mos vs 9.8 mos) compared to those who did not experience an irAE (HR 0.51, 95% CI 0.43–0.76, p=0.011) (figure 1). Landmark survival analyses at 12 and 24 weeks continued to support significant differences in median OS based on presence or absence of an irAE (HR 0.49, 95% CI 0.24–0.46, and HR 0.45, 95% CI 0.21–0.60 respectively). Among patients with at least one irAE, the subset of patients who experienced multiple irAEs had further improved median OS compared to those with a single irAE.ConclusionsIn patients with advanced NSCLC treated with combination ICI plus chemotherapy, the occurrence of an irAE is associated with improved overall survival.ReferencesTeraoka S, Fujimoto D, Morimoto T, et al. Early Immune-related adverse events and association with outcome in advanced non-small cell lung cancer patients treated with Nivolumab: a prospective cohort study. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer 2017;12(12):1798–1805. doi:10.1016/j.jtho.2017.08.022.Ricciuti B, Genova C, De Giglio A, et al. 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. Journal of Cancer Research and Clinical Oncology 2019;145(2):479–485. doi:10.1007/s00432-018-2805-3.Toi Y, Sugawara S, Kawashima Y, et al. Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. The Oncologist. 2018;23(11):1358–1365. doi:10.1634/theoncologist.2017-0384.Shankar B, Zhang J, Naqash AR, et al. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncol 2020;6(12):1952–1956. doi:10.1001/jamaoncol.2020.5012Ethics ApprovalThis research study obtained ethics approval by the institutional review board at the University of Virginia, IRB# 19083.Abstract 803 Figure 1Overall Survival by presence or absence of an irAE in patients with advanced lung cancer treated with immune checkpoint inhibitors plus chemotherapy


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Baha’eddin Muhsen ◽  
Hamid Borghei-Razavi ◽  
Wei Wei ◽  
...  

Abstract INTRODUCTION: Non-small cell lung cancer brain metastases (NSCLCBM) patients have a dismal prognosis. Immune checkpoint inhibitors (ICI) have resulted in improved outcomes in a subset of patients, although limited information exists on the impact of ICI in patients with NSCLCBM. METHODS: We reviewed 121 NSCLCBM (2012–2018) patients treated at our tertiary care center. All patients received at least 2 cycles of ICI therapy after diagnosis of NSCLCBM. Overall survival (OS) and progression-free survival (PFS) were calculated from the start of ICI therapy to date of death, progression or last follow up. Kaplan-Meier curves were used to estimate survival and were analyzed using the Wilcoxon test. RESULTS: Median age was 62 years (39–81) and median KPS was 90. Eighty-six patient received Nivolumab, 7 Atezolizumab, 25 Pembrolizumab, and 3 patients received multiple ICI over the course of their treatment for NSCLCBM. One hundred and twelve patients underwent stereotactic radiosurgery. Nine patients were treated with ICI alone and 25 patients underwent surgical resection. Median OS for the entire cohort was 558 (303–1159) days and median PFS was 220 (114–512) days. Twenty-four patients received oral steroids within the first 28 days of ICI (median prednisone equivalent dose of 27 mg). Patients on upfront steroid therapy had a median PFS of 148 days vs 301 days in patients not on upfront steroids (p-value .0095). Complete blood count at the start of ICI was available for 87 patients and neutrophil to lymphocyte ratios (NLR) were calculated. Patients with NLR at the start of ICI above 5 (n=33) had a median overall survival of 337 days compared to 558 days when NLR was below 5 (p-value .038). CONCLUSION: Use of steroids at initiation or within first 28 days of ICI therapy and NLR of greater than 5 are associated with worse outcomes in NSCLCBM treated with ICI.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jason C. Hsu ◽  
Phung-Anh Nguyen ◽  
Yen-Tzu Chen ◽  
Szu-Chun Yang ◽  
Chien-Chung Lin ◽  
...  

Immune checkpoint inhibitors (ICIs) have been approved to treat patients with various cancer types, including lung cancer, in many countries. This study aims to investigate the effectiveness and safety of ICIs under different treatment conditions of non-small cell lung cancer patients. A population-based retrospective cohort study was conducted using the electronic health records of three medical centers in Taiwan. From January 01, 2016, to November 30, 2018, a total of 91 ICIs and 300 traditional chemotherapy users who had undergone stage III and IV lung cancer treatment were included in the study. We performed the randomized matched pair design by selecting a Chemotherapy subject for each ICI patient in the sample population. All subjects were monitored from the date of taking ICIs or chemotherapy drugs until the event of death, loss to follow-up, or were occurred with any defined adverse events. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the overall survival, efficacy, and safety of the ICIs group. The median overall survival (OS) in the ICI and Chemo groups after matching was 11.2 months and 10.5 months, respectively. However, the results showed no significant OS differences between ICIs and chemo groups for both before and after matching (HR,1.30; 95%CI, 0.68-2.46; p=0.428 before matching and HR,0.96; 95CI%, 0.64-1.44; p=0.838 after matching). We observed that with the higher amount of PD-L1, the length of the patients’ overall survival was (positive vs. negative PD-L1, HR,0.21; 95%CI, 0.05-0.80; p=0.022). The incidences of serious adverse drug events above grade 3 in the ICIs and traditional chemo groups were 12.7% and 21.5%, respectively. We also found that the number of AEs was less in ICIs than in the Chemo group, and the AEs that occurred after treatments were observed earlier in the ICIs compared to the Chemo group. ICIs drugs were observed to be safer than traditional chemotherapy as they had a lower risk of serious adverse drug events. It is necessary to pay attention to immune-related side effects and provide appropriate treatment. Furthermore, the patient’s physical status and PD-L1 test can be used to evaluate the clinical effectiveness of ICIs.


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