Lung cancer and immunotherapy: a real-life experience from second line and beyond

2019 ◽  
Vol 15 (26) ◽  
pp. 3025-3032 ◽  
Author(s):  
Fady El Karak ◽  
Fady Gh Haddad ◽  
Roland Eid ◽  
Maya Al Ghor ◽  
Elie El Rassy ◽  
...  

Aim: This study assessed the efficacy of anti-PD-1/PD-L1 agents in real life when used in second line or beyond. Materials & methods: Patients with advanced non-small-cell lung cancer progressing after standard chemotherapy and receiving immunotherapy in the second line or beyond were included. Results: One hundred and ten patients were included with PD-L1 expression above 50%, between 1–49 and <1% in 38.6, 27.3 and 34.1% of patients, respectively. Checkpoint inhibitors were used as second, third and fourth line in 74.7, 21.8 and 3.5%, respectively. Partial response was observed in 25.6% of patients. Median progression-free survival was 4 months and median overall survival was 8.1 months. Conclusion: Immunotherapies are emerging as important tools in the oncologic field with good responses in real-life practice.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14530-e14530 ◽  
Author(s):  
Stephanie Labomascus ◽  
Ibtihaj Fughhi ◽  
Philip Bonomi ◽  
Mary J. Fidler ◽  
Jeffrey Allen Borgia ◽  
...  

e14530 Background: Baselinehigh neutrophil to lymphocyte ratio (NLR) has been associated with inferior overall survival in patients with stage III/IV NSCLC. Inflammation and neutrophilic infiltrates in the tumor microenvironment appear to inhibit anti-tumor immune response. We suspect that NLR might reflect the level of inflammation in tumor microenvironment. The objectives of this study were to evaluate potential relationships between pretreatment NLR and and PFS and OS in advanced NSCLC patients treated with second-line nivolumab or pembrolizumab. Methods: Patients with stage IV NSCLC who received at least one cycle of nivolumab or pembrolizumab after first-line treatment with a platinum doublet between January 2015 and December 2016 were included. Patient demographics including NLR at baseline, date of starting immunotherapy, and date of progression were recorded. The association between NLR and duration of response was assessed using a Mann-Whitney-Wilcoxon test. A cutoff of NLR of 3.5 and 5.0 based on published data (ref) were analyzed for differences in median overall survival and progression free survival. Results: 113 patients were analyzed: median age 68, male/female 38.9%/61.1%, 15% never smoked. The median PFS for patients with NLR < 5 was 4.14 months vs. 2.27 months in those with NLR > 5 (p = 0.031). Overall survival was also impacted by NLR. There were a total of 29 deaths in the cohort, 24 of these occurred in patients with NLR > 3.5 and 5 were in patients with NLR < 3.5. A lower NLR at baseline was significantly associated with improved overall survival (p = 0.036). Conclusions: A low baseline NLR is associated with superior progression free survival and overall survival in metastatic non-small cell lung cancer patients treated with nivolumab or pembrolizumab. These findings suggest that evaluating mediators of inflammation might help to identify potential therapeutic targets which could enhance effectiveness of PD-1 immune check point inhibitors in advanced NSCLC.


2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 108-108
Author(s):  
Carmen GarcÃa Durán ◽  
Alberto L. Moreno-Vega ◽  
Pedro Sánchez Mauriño ◽  
Javier López-González ◽  
Isidoro C. Barneto - Aranda ◽  
...  

108 Background: Recently, nivolumab has been approval as 2nd-line treatment of non-small cell lung cancer (NSCLC) in our country. Data regarding its effectiveness or safety in real-life setting are publishing daily. Methods: 27 patients with advanced NSCLC treated with nivolumab at HURS between February 2016 to November 2017, were evaluated for survival (overall survival OS, progression-free survival PFS), time to treatment failure (TTF), treatment discontinuation due to toxicity and demographics/clinicopathological characteristics, using SPSS v 8.0. Results: Median age was 62 years; 77,8% males. At closing data, 25,9% of patients were still receiving nivolumab treatment. 51,9 % had finished treatment due to disease progression and 7,4% to toxicity. 25,9% patients continued others chemotherapies schedules. Mean of cycles received was 11. 51,8% presented ORR to nivolumab (78% PR). The median TTF at nivolumab was 3 months. The median progression-free survival (PFS) was 6.93 months (6,2 months in the squamous histology vs 9,42 in adenocarcinoma). The median OS was 22.6 months. Neutrophil-lymphocyte ratio in a complete blood count did not decrease during nivolumab treatment in any patients (p < 0.05, McNemar test), no relation to survival rates (with a cut-off of 5 and 3). Conclusions: Effectiveness (OS and PFS) of nivoumab were high in our patients, slightly better than those observed with similar characteristics included in clinical trials. We have not found predictive survival markers.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21202-e21202
Author(s):  
John P. Palmer ◽  
Yenong Cao ◽  
Samer Ibrahim ◽  
Natasha Dhawan ◽  
Muhammad Zubair Afzal ◽  
...  

e21202 Background: Increased systemic inflammatory state and increased inflammation within tumor micro-environment (TME) have been associated with a worse prognosis and lower responsiveness to immune checkpoint inhibitors (ICI). Systemic inflammatory immune index (SII) reflects the changes in the systemic inflammatory matrix. Studies have shown the association of SII with cancer survival and treatment outcomes. We aim to study the effect of SII on treatment outcomes in non-small cell lung cancer (NSCLC) patients being treated with ICI. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs (pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab) alone or in combination with chemotherapy. SII is the product of platelets multiplied by neutrophils divided by lymphocytes. Baseline and 8-week SIIs were obtained. Radiographic response, duration of radiographic response (date of best response to radiographic progression), overall survival (OS), and progression-free survival (PFS) were evaluated. A high SII was defined as a value greater than the median SII. Cox regression univariate and multivariate analyses were performed. Logistic regression, t-test, and Chi-square tests were applied. Results: Overall, 81% patients had adenocarcinoma and 19% patients had squamous, adenosquamous or large cell carcinoma. The majority of the patients were female (56.2% vs. 43.8%). Median SII at baseline was 1335. The objective response rate (ORR) was 45.1%. The disease control rate was 75.8%. The ORR was 51% in patients receiving ICI first-line compared to 35% in those who received ICI as a second-line therapy. At baseline, there was no difference in the mean SII between responders and non-responders (2146.2 vs. 1917.5, P = 0.5); however at 8 weeks, the mean SII was significantly lower in responders compared to non-responders (1198.8 vs. 2880.2, P = 0.02). A total of 15 (10.9%) patients were found to have pseudoprogression or mixed response on follow-up imaging. Among these, 11(73.3%) patients had low SII at 8 weeks (P = 0.04). The median OS was significantly higher in patients with low SII at baseline (29.6 months vs. 10.1 months, P = 0.001 95% CI 10.6 – 22.1). Similarly, there was a significant difference in median PFS in patients with low SII (14.6 months vs. 6.7 months, P = 0.002, 95% CI 5.6 – 11.6). There was no correlation between high or low SII on the incidence of immune-related adverse events. Conclusions: SII may have significant impact on OS and PFS and could be serially monitored to assess the response to ICI. A low SII may help to differentiate pseudoprogression vs. true progression. Prospective studies are needed to validate these findings. Further, it will be interesting to see if SII could be incorporated into predictive models to determine the duration of cytotoxic therapy in selected patients.


Immunotherapy ◽  
2021 ◽  
Author(s):  
Xingyu Liu ◽  
Huifang Xing ◽  
Hongbing Zhang ◽  
Hongyu Liu ◽  
Jun Chen

Aim: We conducted a systematic review and network meta-analysis to evaluate the efficacy of immunotherapy versus chemotherapy to treat extensive-stage small-cell lung cancer. Methods: We analyzed several eligible clinical trials using fixed or random-effects models to evaluate relative treatment effects depending on heterogeneity. Results: In the experimental group, immunotherapy showed significant improvement in overall survival (hazard ratio [HR]: 0.82; 95% CI: 0.74–0.89; I2 = 31.4%; p < 0.001) and progression-free survival (HR: 0.77; 95% CI: 0.80–0.83; I2 = 22.7%; p < 0.001). Conclusion: Immunotherapy is likely to significantly improve extensive-stage small-cell lung cancer patients' overall survival and progression-free survival compared with standard chemotherapy. Anti-PD L1 exhibited superior overall survival compared with anti-PD 1 and anti-CTLA4.


2012 ◽  
Vol 136 (10) ◽  
pp. 1201-1204 ◽  
Author(s):  
Yung-Jue Bang

Crizotinib (Xalkori), the first inhibitor of both anaplastic lymphoma kinase (ALK) and c-Met receptor kinases, has been approved in the United States, Korea, and other countries for the treatment of ALK-positive non–small cell lung cancer (NSCLC). This approval came within just 4 years of the discovery of rearrangements in the ALK gene in a subset of patients with NSCLC. Oral crizotinib 250 mg twice daily showed excellent efficacy in patients with advanced ALK-positive NSCLC, with objective response rates of 61% and 51% in ongoing phase I and II studies, respectively. Objective response rates of current standard, single-agent, second-line therapies are less than 10%. Median progression-free survival was 10 months (95% confidence interval, 8.2–14.7) in the phase I study expanded cohort and has yet to be reached in the phase II study; progression-free survival with current therapies is less than 3 months. Crizotinib was well tolerated; grade 1/2 gastrointestinal toxicity and visual disturbances were the most common adverse events. Patients in the phase II study reported improvements in fatigue, dyspnea, and cough, based on quality of life assessments. Phase III studies investigating crizotinib for the first- and second-line treatment of advanced ALK-positive NSCLC, versus current standards of care, are ongoing. Crizotinib represents a new standard of care for patients with ALK-positive NSCLC and highlights the importance of the role of the pathologist, as molecular profiling becomes a part of initial workups for newly diagnosed patients with NSCLC. This approach will ensure effective individualized treatment for patients with NSCLC.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14135-e14135
Author(s):  
Emanuela Romano ◽  
Roberta Poli ◽  
Clement Dumont ◽  
Lisa Pietrogiovanna ◽  
Marie Vigan ◽  
...  

e14135 Background: Immune checkpoint inhibitors (ICIs) are approved for the treatment of non-small cell lung cancer (NSCLC) and are associated with immune-related adverse events (irAEs). However, real-life data on type, occurrence and kinetics of irAEs, and their predictive value on treatment outcome are lacking. Here, we report on the relation between irAEs, including endocrine irAEs, and outcome to anti-PD-/L-1 (programmed cell death protein-/ligand-1) ICIs. Methods: A total of 147 patients (pts), with locally advanced/metastatic NSCLC, treated with anti-PD-1 (N 140; 95%) or anti-PD-L1 agents (N 7; 5%) as ≥ 2 line treatment were included in two independent, prospective, cohorts at the Institut Curie (ALCINA-NCT02866149) and at Biella Hospital (Italy). PD-L1 status was assessed by immunohistochemistry (clone 22C3, Dako). Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier curves. Results: Median follow-up of 147 pts was 10.2 (range: 0.7-42.8) months; median age, 66 (35-85) years; 100 men (68%). After treatment initiation, irAEs were observed in 72 pts (49%). Thirty one (43%) pts had only endocrine irAEs, mostly thyroid dysfunctions (N 44, 61%). Pre-existing thyroid disease was present in only 6 pts (4%). Dermatologic toxicity in 21 (29%) pts was the next most frequent irAE, 22 (30%) pts had other types of irAEs. Among patients with irAEs, 61 (85%) had ≤ 2 coexisting irAEs, and 13 (18%) pts had > 2 irAEs. Most irAEs were G1 (63%) and G2 (18%). Onset and kinetics differed according to irAE type. There was no association between PD-L1 status and irAE occurrence. Median PFS was 7.2 and 4.2 months in irAEs vs no-irAEs group, respectively [HR 0.70 (95% CI 0.46;1.08), p 0.11]. Median OS in the irAEs group was 18.1 months vs 13.6 months no-irAEs group [HR 0.64 (95% CI 0.37;0.98), p 0.039]. Median OS in the endocrine-irAEs group was 23.5 vs 13.6 months in the no-irAEs group [HR 0.58 (0.74;3.92), p 0.2]. Conclusions: In this study, we show that irAEs – including endocrine type – are frequent in NSCLC pts treated with ICIs and that their occurrence is associated with a survival benefit.


Sign in / Sign up

Export Citation Format

Share Document