P1.15-03 Clinical Characteristics of Long-Term Survivors With Nivolumab in Pretreated Advanced NSCLC from Real-World Data (RWD) (original) (raw)
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Journal of Thoracic Oncology, 2017
Background: Survival data with nivolumab are based on selected populations and might not reflect outcomes in clinical practice. Overall Survival (OS) and Progression Free Survival (PFS) with anti-PD1 therapy in a large population of unselected patients with advanced Non-Small-Cell-Lung Cancer (NSCLC) are not well documented. We aimed to assess survival data with nivolumab in a large cohort of unselected patients and association of OS with clinical and biological factors. Method: Clinical and survival data were collected in a cohort of NSCLC patients treated with nivolumab who experienced confirmed progressive disease (PD) after 1 line of chemotherapy (CT). Patients received nivolumab at a dose of 3 mg/kg every 2 weeks until PD or unacceptable toxicity. Nivolumab benefit was analyzed according to PFS and OS. The overall response rate (ORR) was analyzed by RECIST 1.1. Age, response to prior CT, eosinophil counts (Ec), prior radiotherapy (RT), lymphocyte counts (Lc), neutrophil counts (Nc), LDH rate were assessed. Kaplan-Meier and Cox regression were performed. Result: 257 patients treated with nivolumab were enrolled from 9 centers between Sept. 2015 and Oct. 2016. Median age was 62 years [29-85]; 186 patients were males (72%), 93% PS1 at the time of the diagnostic; 220 (86%) smokers; 219 (85%) stage IV; 130 patients (51%) received prior RT. 163 patients (63%) had adenocarcinoma, 70 (27%) squamous cells carcinoma ; 54 (21%) were KRASmut, 11 (4%) EGFRmut, 3 (1%) ALKpositive. PD-L1 expression was unknown (test not required in current practice for nivolumab). The median of prior lines was 1 [1-6]. Median PFS with nivolumab was 3 months [1,9-4]. Median OS was 15 months [1-; NR]. The ORR was 23% (58 patients), the disease control rate was 42% (109 patients). The median duration of response was 6 months [1-;16]. Age (> or < 70) (p¼0.202), response to prior CT (p¼0.05) and Ec 0.5 G/l (p¼0.606) were not significantly associated with improved OS. Prior RT was significantly associated with poor OS (p¼0.004). Lc < 1 G/l (p¼0.019), Nc 7 G/l (p¼0.018), LDH 500 U/l (p¼0.008), were significantly associated with poor OS. Conclusion: 1) Efficacy of nivolumab in real life is the same as reported in published studies with a median OS of 15 months in clinical practice. 2) In our study neutrophil, lymphocyte and LDH rates predict a poor OS.
Monitoring blood biomarkers to predict nivolumab effectiveness in NSCLC patients
Therapeutic Advances in Medical Oncology
Background: We investigated whether early dynamic changes of circulating free (cfDNA) levels as well as the neutrophil to lymphocyte ratio (NLR) could predict nivolumab effectiveness in pretreated patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 45 patients receiving nivolumab 3 mg/kg every 2 weeks were enrolled. Patients underwent a computed tomography scan and responses were evaluated by the response evaluation criteria in solid tumors. Peripheral blood samples were obtained from the patients and the cfDNA level as well as the NLR were assessed. Time to progression (TTP) and overall survival (OS) were determined. Results: Patients with increased cfDNA >20% at the sixth week reported significantly worse survival outcomes (median OS: 5.7 versus 14.2 months, p < 0.001; median TTP: 3.3 versus 10.2 months, p < 0.001), as well as patients with increased NLR >20% (median OS: 8.7 versus 14.6 months, p = 0.035; median TTP: 5.2 versus 10.3 months, p = 0.039). The combined increase of cfDNA and NLR >20% was associated with significantly worse survival outcomes as compared with the remained population (median OS: 5.8 versus 15.5 months, p = 0.012; median TTP: 3.2 versus 11.9 months, p = 0.028). Multivariable analysis identified three significant factors associated with worse OS: combined cfDNA/NLR increase >20% [hazard ratio (HR): 5.16; 95% confidence interval (CI), 1.09-24.29; p = 0.038], liver metastasis (HR: 0.44; 95% CI, 0.20-0.96; p = 0.038), and extra-thoracic disease (HR: 0.33; 95% CI, 0.12-0.89; p = 0.029). Conclusion: An early combined increase of both cfDNA and NLR over the course of the first 6 weeks of nivolumab therapy predicted worse survival in pretreated patients with advanced NSCLC, suggesting a potential role in the real-time monitoring of immunotherapy resistance.
Respiratory Medicine and Research, 2020
Background.-Immune checkpoint inhibitors (ICI) are now widely used at different stages of non-small cell lung cancers (NSCLC). Some clinical studies suggest that chemotherapy and immunotherapy have synergic activities, raising the question of the best therapeutic sequence. We studied the effect of chemotherapy in advanced NSCLC when administered after immunotherapy by nivolumab. Methods.-We performed a bicentric, retrospective, case-control study in two French hospitals. Patients with NSCLC treated with chemotherapy after nivolumab between January 2015 and January 2016 were included. Each case was matched on age and number of previous lines to one lung cancer patient who had not received nivolumab. Each CT-scanner has been reviewed and the objective response to chemotherapy was assessed for each patient according to the RECIST 1.1 criteria. Results.-Thirty-one patients with advanced NSCL who had at least received one cycle of chemotherapy after progression under nivolumab in the inclusion period were matched to 31 controls. The median age for cases was 59 yo and the predominant tumoral histology was adenocarcinoma (77%). The progression free survival (PFS) was 2.95 months in the studied group vs 2.69 months (P = 0.18) in the control group. At best response, disease control (DC = partial response and stable disease) was better in the case group than in the control group (58% vs 39%, P = 0.127). Cases were about five times more likely to get objective response to best evaluation than controls (OR = 5.043 [95% CI: 0.975-26.086]; P = 0.054). The overall survival (OS) was 7.3 months in the case group and 3.3 months in the control group (P = 0.074). Patients who have been treated with targeted therapy instead of chemotherapy and patients with squamous lung cancer had worst PFS and OS. Conclusion.-In advanced NSCLC, the chemotherapy progression free survival does not seem higher when administered after nivolumab. However, when administered post-nivolumab, traditional chemotherapy has 5 times more chances to achieve objective response and seems to improve overall survival of cases. Pooled analysis with other similar studies might be interesting for a next step.
Cancer Immunology, Immunotherapy, 2021
Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab...
Journal of Cancer Research and Clinical Oncology, 2018
Purpose Immune-checkpoint inhibitors (ICIs) represent the standard of care for platinum-pretreated advanced non-small cell lung cancer patients. Patients treated with ICIs may experience immune-related adverse events (irAEs), that might reflect antitumor responses. Here we evaluated nivolumab efficacy according to the development of irAEs. Methods We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017. IrAEs were defined as AEs having immunological basis that required intensive monitoring and interventions. Results Among 195 patients [median (range) age, 63 (30-84) years; 128 men (65.6%), 67 women (34.4%)], irAEs were observed in 85 patients (43.6%), including 15 patients (7.6%) with grade 3 or 4 events. Median PFS was 5.7 months in irAEs group compared to 2.0 months of no-irAEs group [HR: 0.41 (95% CI 0.3-0.57), P < 0.0001]. Median OS was 17.8 months compared to 4.0 months of no-irAEs group [HR: 0.33 (95% CI 0.23-0.47), P < 0.0001]. IrAEs were significantly associated with improved clinical outcome in 12-and 6-week landmark analysis. Patients who developed ≥ 2 irAEs during treatment (n: 37) had a significantly longer median PFS and OS compared to those with one (n: 48) or none AEs (n: 110) (PFS: 8.5 months vs. 4.6 vs. 2.0, P < 0.0001; OS: 26.8 months vs. 11.9 vs. 4.0, P < 0.0001). Multivariable analysis revealed that irAEs were positively associated with PFS [HR: 0.48 (95% CI 0.34-0.67), P < 0.0001] and OS [HR: 0.38 (95% CI 0.26-0.56), P < 0.0001]. Conclusion In this study we confirmed that the development of irAEs was a strong predictor of survival outcomes in NSCLC patients treated with nivolumab monotherapy in landmark and multivariable models. Patients who experienced ≥ 2 irAEs had a more pronounced survival benefit compared to those with 1 irAE further suggesting a mechanistic association between irAEs and immunotherapy efficacy.
First-Line Nivolumab in Stage IV or Recurrent Non–Small-Cell Lung Cancer
New England Journal of Medicine, 2017
BACKGROUND Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. METHODS We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. RESULTS Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P = 0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatmentrelated adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy. CONCLUSIONS Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533.