Long-term Overall Survival and Predictors in Anti–PD-1-naive Melanoma Patients With Brain Metastases Treated With Immune Checkpoint Inhibitors in the Real-world Setting

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Girish S. Naik ◽  
Elizabeth I. Buchbinder ◽  
Justine V. Cohen ◽  
Michael P. Manos ◽  
Alistair E.W. Johnson ◽  
...  
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.


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]


Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1940 ◽  
Author(s):  
Maartje G. Schouwenburg ◽  
Karijn P.M. Suijkerbuijk ◽  
Rutger H.T. Koornstra ◽  
Anouk Jochems ◽  
Michiel C.T. van Zeijl ◽  
...  

The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (≥2× upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4–5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Mayur Sharma ◽  
Baha’eddin Muhsen ◽  
Addison Barnett ◽  
...  

AbstractSteroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient’s NLR. In a subgroup analysis, only in patients with NLR < 4 was there a significant difference in OS with upfront steroids (26.1 vs. 15.6 months, p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.


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