Phase 1 cohort expansion study of LY3023414, a dual PI3K/mTOR inhibitor, in patients with advanced mesothelioma.

BACKGROUND LY3023414 is a selective, ATP competitive inhibitor of class I PI3K isoforms, mTORC1/2 and DNA-PK. A Phase 1 dose escalation, 200 mg twice daily (BID) of LY3023414 was the determined recommended phase 2 dose (RP2D). We report the antitumor activity and safety of LY3023414 monotherapy in patients with advanced mesothelioma.METHODS Patients enrolled had advanced malignant pleural or peritoneal mesothelioma with measurable disease, ECOG PS 0-1, were refractory or ineligible to receive standard therapies. Patients received LY3023414 200 mg BID. This dose expansion cohort is intended to evaluate preliminary antitumor activity of LY3023414 by overall response rate. Safety, tolerability and pharmacokinetics were assessed. Biomarkers associated with treatment response was an exploratory endpoint. RESULTS Forty-two patients received LY3023414 for a median duration of 11.2 weeks (range: 1.1-53.0). One patient had a confirmed partial response (PR) (ORR 2.4%). Three patients had an unconfirmed PR. Seventeen patients had stable disease (SD) (DCR 43%). Most common adverse events (AEs) included fatigue (43%), nausea (43%), decreased appetite (38%), vomiting (33%), and diarrhea (29%). AEs were mostly mild or moderate. Grade ≥ 3 AEs were reported for 21% of patients with fatigue as the most frequent event (10%). Alterations of BAP1 were identified in 11/19 patients as the most common molecular aberration, followed by SETD2 and NF2 alterations. No obvious pattern of genetic changes/mutations in single genes or pathways was associated with anti-tumor activity. CONCLUSION LY3023414 monotherapy (200 mg BID) demonstrated an acceptable and manageable safety profile with limited single-agent activity in patients with advanced mesothelioma. ClinicalTrials.gov identifier: NCT01655225; Date of registration: 19 July 2012.

Phase I Study of Intrapleural Gene-Mediated Cytotoxic Immunotherapy in Patients with Malignant Pleural Effusion.

Gene-mediated cytotoxic immunotherapy (GMCI) is an immune strategy implemented through local delivery of an adenovirus-based vector expressing the thymidine kinase gene (aglatimagene besadenovec, AdV-tk) followed by anti-herpetic prodrug valacyclovir. A phase I dose escalation trial of GMCI followed by chemotherapy was conducted in patients with malignant pleural effusion (MPE). AdV-tk was administered intrapleurally (IP) in three cohorts at a dose of 1 × 1012 to 1013 vector particles. Primary endpoint was safety; secondary endpoints included response rate, progression-free survival, and overall survival. Nineteen patients were enrolled: median age 67 years; 14 with malignant mesothelioma, 4 non-small-cell lung cancer (NSCLC), and 1 breast cancer. There were no dose limiting toxicities. All 3 patients in cohort 2 experienced transient cytokine release syndrome (CRS). Addition of celecoxib in cohort 3 reduced the incidence and severity of CRS (none > grade 2). Three patients are alive (23-33 months after GMCI), and 3 of 4 NSCLC patients had prolonged disease stabilization; one is alive 29 months after GMCI, 3.6 years after initial diagnosis. GMCI was safe and well tolerated in combination with chemotherapy in patients with MPE and showed encouraging response. Further studies are warranted to determine efficacy.

Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial.

BACKGROUND: Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort. METHODS: Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries. Patients received pembrolizumab (10 mg/kg every 2 weeks) for up to 2 years or until confirmed progression or unacceptable toxicity. Key eligibility criteria included measurable disease, failure of standard therapy, and Eastern Cooperative Oncology Group performance status of 0 or 1. PD-L1 positivity was defined as expression in 1% or more of tumour cells by immunohistochemistry. Response was assessed based on investigator review using the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Primary endpoints were safety and tolerability, analysed in the all-patients-as-treated population, and objective response, analysed for the full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT02054806, and is ongoing but not recruiting participants. FINDINGS: As of June 20, 2016, 25 patients received pembrolizumab. 16 (64%) patients reported a treatment-related adverse event; the most common adverse event were fatigue (six [24%]), nausea (six [24%]), and arthralgia (five [20%]). Five (20%) patients reported grade 3 treatment-related adverse events. Three (12%) patients required dose interruption because of immune-related adverse events: one (4%) of 25 each had grade 3 rhabdomyolysis and grade 2 hypothyroidism; grade 3 iridocyclitis, grade 1 erythema multiforme, and grade 3 erythema; and grade 2 infusion-related reaction. No treatment-related deaths or discontinuations occurred. Five (20%) patients had a partial response, for an objective response of 20% (95% CI 6·8-40·7), and 13 (52%) of 25 had stable disease. Responses were durable (median response duration 12·0 months [95% CI 3·7 to not reached]); two patients remained on treatment at data cutoff. INTERPRETATION: Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma. Response durability and efficacy in this patient population warrants further investigation. FUNDING: Merck.

Sotorasib as First-Line Treatment for Advanced KRAS G12C-Mutated Non-Small Cell Lung Carcinoma: A Case Report.

Mutations in the KRAS gene are the most common gain-of-function mutations found in lung adenocarcinomas. The most common mutation, KRAS G12C, is present in 13% of lung adenocarcinomas. Sotorasib (AMG-510) is an irreversible small molecule inhibitor targeting KRAS G12C. In preclinical studies, treatment with sotorasib led to the regression of KRAS G12C-mutated tumors, and clinical efficacy in NSCLC was demonstrated in clinical trials. In May 2021, sotorasib received US FDA approval for treatment of KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. In this report, we present a case with metastatic, KRAS G12C-mutated NSCLC who responded favorably to sotorasib as first-line therapy. The efficacy of sotorasib as first-line treatment in this patient was remarkable, which supports further study of sotorasib as first-line therapy for KRAS G12C-mutated NSCLC, especially in fragile patients with comorbidities.

Meta-Analysis of Survival and Development of a Prognostic Nomogram for Malignant Pleural Mesothelioma Treated with Systemic Chemotherapy.

(1) Purpose: Malignant pleural mesothelioma (MPM) is a rare cancer with an aggressive course. For patients who are medically inoperable or surgically unresectable, multi-agent systemic chemotherapy remains an accepted standard-of-care. The purpose of this meta-analysis is to provide baseline summative survival estimates as well as evaluate the influence of prognostic variables to provide comparative estimates for future trial designs. (2) Methods: Using PRISMA guidelines, a systematic review and meta-analysis was performed of MPM studies published from 2002-2019 obtained from the Medline database evaluating systemic therapy combinations for locally advanced or metastatic disease. Weighted random effects models were used to calculate survival estimates. The influence of proportions of known prognostic factors on overall survival (OS) were evaluated in the creation of a prognostic nomogram to estimate survival. The performance of this model was evaluated against data generated from one positive phase II study and two positive randomized trials. (3) Results: Twenty-four phase II studies and five phase III trials met the eligibility criteria; 2534 patients were treated on the included clinical studies. Ten trials included a platinum-pemetrexed-based treatment regimen, resulting in a pooled estimate of progression-free survival (PFS) of 6.7 months (95% CI: 6.2-7.2 months) and OS of 14.2 months (95% CI: 12.7-15.9 months). Fifteen experimental chemotherapy regimens have been tested in phase II or III studies, with a pooled median survival estimate of 13.5 months (95% CI: 12.6-14.6 months). Meta-regression analysis was used to estimate OS with platinum-pemetrexed using a variety of features, such as pathology (biphasic vs. epithelioid), disease extent (locally advanced vs. metastatic), ECOG performance status, age, and gender. The nomogram-predicted estimates and corresponding 95% CIs performed well when applied to recent randomized studies. (4) Conclusions: Given the rarity of MPM and the aggressive nature of the disease, innovative clinical trial designs with significantly greater randomization to experimental regimens can be performed using robust survival estimates from prior studies. This study provides baseline comparative values and also allows for accounting for differing proportions of known prognostic variables.

CT for detection of malignant posterior intercostal lymph nodes in patients undergoing pre-operative staging for malignant pleural mesothelioma.

INTRODUCTION: Recent evidence suggests that patients with malignant pleural mesothelioma (MPM) undergoing extended pleurectomy/decortication (eP/D) with metastasis to the posterior intercostal lymph nodes (PILN) have a worse prognosis. In this study, we determine if MPM PILN metastasis can be reliably detected on computed tomography (CT). MATERIALS AND METHODS: Preoperative staging CT exams were reviewed for the presence of PILN in MPM patients undergoing eP/D between 2007-2013 with surgical sampling of their PILN. CT images were reviewed by two thoracic radiologists blinded to clinical records, including operative pathology reports. The number and short axis size of PILN were recorded and correlated with surgical pathology. Statistical analysis examined the value of preoperative CT to detect metastatic PILN. RESULTS: Of 36 patients that underwent eP/D with PILN sampling had preoperative CT images for review. At surgery, 22 of these patients had metastatic PILN and 14 had benign PILN. The positive and negative predictive values for one or more nodes seen on preoperative CT were 60 % and 38 % respectively. The number of PILN on preoperative CT did not predict metastasis (p = 0.40) with an average of 2 PILN seen, regardless of PILN pathology. The average nodal short axis size was 4.6 mm and 4.8 mm for benign and malignant PILN, respectively, and PILN short axis size did not predict metastasis (p = 0.39). There was little inter-observer variability between the size and number of nodes detected by each radiologist. CONCLUSIONS: CT does not reliably identify metastatic PILN on preoperative CT for patients with MPM undergoing extended pleurectomy/decortication.

Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial.

OBJECTIVES: Soluble mesothelin-related protein (SMRP) and fibulin-3 serum levels may serve as diagnostic and prognostic biomarkers of malignant pleural mesothelioma (MPM). Here, we evaluate these markers for correlation to tumor volume, prognosis and response assessment in a clinical trial of immunogene therapy in combination with chemotherapy. MATERIALS AND METHODS: Serial serum levels of SMRP and fibulin-3 were measured in adult patients with biopsy-proven MPM enrolled in two prospective clinical trials. Pre-therapy computed tomography (CT) measurements of tumor burden were calculated and correlated with pre-therapy serum SMRP and fibulin-3 levels in these two trials. Serological data were also correlated with radiological assessment of response using Modified RECIST criteria over the first 6 months of intrapleural delivery of adenovirus-IFN alpha (Ad.IFN-α) combined with chemotherapy. RESULTS: A cohort of 58 patients who enrolled in either a photodynamic therapy trial or immunotherapy clinical trial had available imaging and SMRP serological data for analysis of whom 45 patients had serological fibulin-3 data. The cohort mean total tumor volume was 387 cm3 (STD 561 cm3). Serum SMRP was detectable in 57 of 58 patients (mean 3.8 nM, STD 6.0). Serum fibulin-3 was detected in 44 of 45 patients (mean 23 ng/mL, STD 14). At pre-therapy baseline in these two trials, there was a strong correlation between tumor volume and serum SMRP levels (r = 0.61, p < 0.001), and a moderate correlation between tumor volume and serum fibulin-3 levels (r = 0.36, p = 0.014). Twenty-eight patients in the immunotherapy trial had longitudinal serologic and radiographic data. Fold-changes in SMRP and fibulin-3 did not show significant correlations with modified RECIST measurements. CONCLUSIONS: Although our data show correlations of SMRP and fibulin-3 with initial tumor volumes as measured by CT scanning, the use of SMRP and fibulin-3 as serological biomarkers in the immunotherapy trial were not useful in following tumor response longitudinally.

Lymphangitic carcinomatosis: A common radiographic manifestation of local failure following extended pleurectomy/decortication in patients with malignant pleural mesothelioma.

INTRODUCTION: The lymphangitic carcinomatosis (LC) pattern of metastatic malignancy is associated with a poor prognosis but is currently not well defined in malignant pleural mesothelioma (MPM). Here, we report the incidence and prognostic significance of the radiographic development of LC in MPM following extended pleurectomy/decortication (EPD). METHODS: Consecutive patients with biopsy-proven MPM undergoing EPD with intraoperative photodynamic therapy (PDT) at our institution from 2008 to 2014 were included in this retrospective study. Patients without available post-surgical clinical or imaging data for direct review were excluded. CT images were reviewed by an experienced, board-certified thoracic radiologist and confirmed by consensus review. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan Meier methodology. Hazard ratios were compared with a cox proportional hazard model. RESULTS: 44 patients underwent EPD with PDT during the study period and had available clinical and imaging data. During the follow-up period (median 34 months), 17 patients (39%) developed LC at a median of 10 months after surgery (IQR 5-21 months). 16 of the 17 patients who developed LC (94%) died during the follow-up period, compared to 17 of the 27 who did not develop LC (63%). OS for the LC versus non-LC group was 53% versus 93% at 1 year and 18% versus 67% at 3 years. LC was significantly associated with a lower OS (HR 4.07; 95% confidence interval 1.44-11.48; p = 0.008). PFS for the LC group versus non-LC group was 8 months (IQR 5-9 months) compared to 17 months (IQR 11-24 months) (p < 0.001). CONCLUSION: LC is a common form of failure in MPM following EPD and is associated with a poor prognosis. Thus, further studies are warranted to determine if any evidence of preoperative LC should be an absolute contraindication to EPD and may warrant an EPP or no surgery at all.

Impact of KRAS and TP53 Co-Mutations on Outcomes After First-Line Systemic Therapy Among Patients With STK11-Mutated Advanced Non-Small-Cell Lung Cancer.

PURPOSE: The STK11 gene encodes a serine/threonine protein kinase that regulates cell polarity and functions as a tumor suppressor. Patients with non-small-cell lung cancer (NSCLC) and STK11 mutations often have other co-mutations. We evaluated the impact of KRAS and TP53 co-mutations on outcomes after first-line systemic therapy for patients with metastatic or recurrent NSCLC that harbors STK11 mutations. METHODS: We conducted a retrospective review of patients with metastatic NSCLC and STK11 mutations treated at the University of Pennsylvania. STK11 mutations were identified through next-generation sequencing (NGS) in tissue or plasma. Cox proportional hazard models were used to determine the relationship between STK11 co-mutations and survival outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). RESULTS: From February 2013 to December 2016, samples from 1,385 patients with NSCLC were analyzed by NGS; of these, 77 patients (6%) harbored an STK11 mutation (n = 56, tissue; n = 21, plasma). Of the 62 patients included, 18 had an STK11 mutation alone, 19 had STK11/KRAS, 18 had STK11/TP53, and seven had STK11/KRAS/TP53. Patients with STK11/KRAS co-mutations had a worse median PFS (2.4 months) compared with STK11 alone (5.1 months; log-rank P = .048), STK11/TP53 (4.3 months; log-rank P = .043), and STK11/KRAS/ TP53 (13 months; log-rank P = .03). Patients with STK11/KRAS co-mutation experienced shorter median OS (7.1 months) compared with STK11 alone (16.1 months; log-rank P < .001), STK11/TP53 (28.3 months; log-rank P < .001), and STK11/KRAS/TP53 (22 months; log-rank P = .025). CONCLUSION: Among patients with advanced NSCLC and STK11 mutations treated with first-line systemic therapy, co-mutation with KRAS was associated with significantly worse PFS and OS. By contrast, co-mutation of STK11 with TP53 conferred a better prognosis.

Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non-Small Cell Lung Cancer.

Importance: The clinical implications of adding plasma-based circulating tumor DNA next-generation sequencing (NGS) to tissue NGS for targetable mutation detection in non-small cell lung cancer (NSCLC) have not been formally assessed. Objective: To determine whether plasma NGS testing was associated with improved mutation detection and enhanced delivery of personalized therapy in a real-world clinical setting. Design, Setting, and Participants: This prospective cohort study enrolled 323 patients with metastatic NSCLC who had plasma testing ordered as part of routine clinical management. Plasma NGS was performed using a 73-gene commercial platform. Patients were enrolled at the Hospital of the University of Pennsylvania from April 1, 2016, through January 2, 2018. The database was locked for follow-up and analyses on January 2, 2018, with a median follow-up of 7 months (range, 1-21 months). Main Outcomes and Measures: The number of patients with targetable alterations detected with plasma and tissue NGS; the association between the allele fractions (AFs) of mutations detected in tissue and plasma; and the association of response rate with the plasma AF of the targeted mutations. Results: Among the 323 patients with NSCLC (60.1% female; median age, 65 years [range, 33-93 years]), therapeutically targetable mutations were detected in EGFR, ALK, MET, BRCA1, ROS1, RET, ERBB2, or BRAF for 113 (35.0%) overall. Ninety-four patients (29.1%) had plasma testing only at the discretion of the treating physician or patient preference. Among the 94 patients with plasma testing alone, 31 (33.0%) had a therapeutically targetable mutation detected, thus obviating the need for an invasive biopsy. Among the remaining 229 patients who had concurrent plasma and tissue NGS or were unable to have tissue NGS, a therapeutically targetable mutation was detected in tissue alone for 47 patients (20.5%), whereas the addition of plasma testing increased this number to 82 (35.8%). Thirty-six of 42 patients (85.7%) who received a targeted therapy based on the plasma result achieved a complete or a partial response or stable disease. The plasma-based targeted mutation AF had no correlation with depth of Response Evaluation Criteria in Solid Tumors response (r = -0.121; P = .45). Conclusions and Relevance: Integration of plasma NGS testing into the routine management of stage IV NSCLC demonstrates a marked increase of the detection of therapeutically targetable mutations and improved delivery of molecularly guided therapy.

Immunotherapy and radiation therapy for malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a particularly aggressive thoracic malignancy with limited survival following combination chemotherapy. As a result, there has been increased interested in immunotherapy for mesothelioma, both in the first-line and salvage settings. Early investigations of interleukin-2 (IL-2) and interferon alfa-2a/b have been limited by modest response rates and toxicity, whereas cytokine gene therapy is currently being investigated and shows early promise. The most prominent class of immunotherapies to be trialed with mesothelioma in the past half-decade has been immune checkpoint inhibitors (CPI). Early results are encouraging, particularly for agents targeting the PD-1/PD-L1 pathways. With the increasing recognition of the immune potential of mesothelioma, interest in the immunomodulatory properties of radiation therapy has emerged. The combination of immunotherapy and radiation therapy may allow for complimentary immunologic effects that can enhance antitumor response. This article reviews the existing literature on the efficacy of immunotherapy for MPM, describes the rationale for combining immunotherapy with radiation therapy, and discusses early literature on this treatment combination.

Pretreatment Red Blood Cell Total Folate Concentration Is Associated With Response to Pemetrexed in Stage IV Nonsquamous Non-Small-cell Lung Cancer.

INTRODUCTION: Pemetrexed inhibits folate-dependent enzymes involved in pyrimidine and purine synthesis. Previous studies of genetic variation in these enzymes as predictors of pemetrexed efficacy have yielded inconsistent results. We investigated whether red blood cell (RBC) total folate, a phenotypic rather than genotypic, marker of cellular folate status was associated with the response to pemetrexed-based chemotherapy in advanced nonsquamous non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We conducted a prospective cohort study of patients with stage IV nonsquamous NSCLC receiving first-line chemotherapy containing pemetrexed. The pretreatment RBC total folate level was quantified using liquid chromatography mass spectrometry. We then compared the objective response rate (ORR) between patients with RBC total folate concentrations greater than and less than an optimal cutoff value determined from the receiver operating characteristic curve. A logistic regression model was used to adjust for age, sex, and the use of bevacizumab. RESULTS: The ORR was 62% (32 of 52 patients). Receiver operating characteristic analysis was used to establish that a RBC total folate cutoff value of 364.6 nM optimally discriminated between pemetrexed responders and nonresponders. Patients with RBC total folate < 364.5 nM had an ORR of 27% compared with 71% for patients with RBC total folate > 364.5 nM (P = .01). This difference persisted after adjusting for age, sex, and the use of bevacizumab (odds ratio, 0.07; 95% confidence interval, 0.01-0.57; P = .01). CONCLUSION: A low pretreatment RBC total folate was associated with an inferior response to pemetrexed-based chemotherapy in stage IV nonsquamous NSCLC. Larger, multicenter studies are needed to validate RBC total folate as a predictive marker of pemetrexed response.

The value of delayed phase enhanced imaging in malignant pleural mesothelioma.

BACKGROUND: Cross-sectional imaging of malignant pleural mesothelioma (MPM) can underestimate the presence of local tumor invasion. Since accurate staging is vital optimal choice of therapy, techniques that optimize pleural imaging are needed. Here we estimate the optimal timing of MPM enhancement on magnetic resonance imaging (MRI). METHODS: All MPM patients with intravenous (IV) contrast enhanced staging MRI between 2000-2016 at our institution were retrospectively selected for image analysis. Patients with incomplete imaging protocol and maximum pleural tumor thickness <1 cm were excluded. Quantitative measurements of tumor signal intensity were obtained on pre-contrast and post-contrast phases where MRI acquisition parameters were fixed. Using best-fit model curves, predicted maximum time points of enhancement were determined using a simulation of predicted values. Additionally, a qualitative assessment of tumor conspicuity was performed at all IV contrast time delays imaged. A statistical analysis assessed for correlation between qualitative lesion conspicuity and quantitative tumor enhancement. RESULTS: Of the 42 MPM patients who had undergone staging MRI during the study period, 12 patients met the study criteria. Peak tumor enhancement was between 150 and 300 sec following IV contrast administration. Within this time window, 80% of patients are projected to have reached >80%, >85%, and >90% peak tumor enhancement. There was a statistically significant correlation between increasing tumor enhancement and subjective lesion conspicuity. CONCLUSIONS: Optimal MPM enhancement on MRI likely occurs at a time delay between 2.5-5 min following IV contrast administration. Further study of delayed phase enhancement of MPM with dynamic contrast enhanced MRI is warranted.

Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer.

OBJECTIVES: Efficient use of nivolumab in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. In patients with metastatic melanoma treated with ipilimumab, a pretreatment neutrophil-to-lymphocyte ratio (NLR)<5 has been associated with improved survival. This retrospective cohort study aimed to determine whether the pretreatment NLR was associated with outcomes in NSCLC patients treated with nivolumab. METHODS: We reviewed the medical records of all patients with previously treated advanced NSCLC who received nivolumab between March 2015 and March 2016 outside of a clinical trial at the University of Pennsylvania. Patients were dichotomized according to pretreatment NLR<5 vs. ≥5. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment NLR on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). RESULTS: 175 patients were treated. Median age was 68 (range, 33-88); 54% were female. Twenty-five percent of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2; 46% had received ≥2 prior systemic therapies. In multivariate analyses, pretreatment neutrophil-to-lymphocyte ratio (NLR) ≥5 was independently associated with inferior OS (median 5.5 vs. 8.4 months; HR 2.07, 95% CI 1.3-3.3; p=0.002) and inferior PFS (median 1.9 vs. 2.8 months; HR 1.43, 95% CI 1.02-2.0; p=0.04). CONCLUSIONS: In a cohort of patients with NSCLC treated with nivolumab in routine practice, pretreatment NLR≥5 was associated with inferior outcomes. It is unclear whether this marker is predictive or prognostic. Prospective studies are warranted to determine the utility of NLR in the context of other biomarkers of programmed death-1 (PD-1) therapy.