Neutrophil to lymphocyte ratio, PD-L1 expression, and survival in patients with advanced non-small cell lung cancer receiving first-line immune checkpoint inhibitor therapy.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 46-46
Author(s):  
Mingjia Li ◽  
Songzhu Zhao ◽  
Daniel Spakowicz ◽  
Jarred Thomas Burkart ◽  
Sandip H. Patel ◽  
...  

46 Background: Neutrophil to lymphocyte ratio (NLR) is known to be prognostic for patients with various types of cancer, including those who are treated with immune checkpoint inhibitors (ICI). We evaluated NLR at baseline and during early phase of treatment for patients with advanced non-small cell lung cancer (NSCLC) who received ICI to evaluate its prognostic value in first line ICI therapy and its relationship to programmed death-ligand 1 (PD-L1) expression. Methods: We retrospectively evaluated patients with advanced NSCLC who received ICI as first line therapy from 2016 to 2018. NLR was calculated as ratio of absolute neutrophil/lymphocyte counts and was consider elevated if ≥5. PD-L1 expression by immunohistochemistry was performed as standard of care with 22C3 antibody. Kaplan Meier analysis was used for survival. Wilcoxon-Mann-Whitney test was used to evaluate PD-L1 expression between groups. All Calculation was performed using SAS V9.4. Results: A total of 78 patients were included in this study; 28 received pembrolizumab monotherapy, 45 received pembrolizumab, carboplatin, and pemetrexed, and 5 received other pembrolizumab combinations. Patients with baseline NLR < 5 before initiating ICI had median estimated OS of 46.1 months (79.4% patient still alive and 95% CI not reached) compare to median OS of 10.7 months (95% CI lower limit 6.4 and upper limit not reached) for patients with NLR ≥5, P < 0.001. Similar association between NLR and OS can be seen when NLR were repeated immediate before the cycle 2 with P = 0.001. We observed an association between baseline NLR and PD-L1 expression. The median PD-L1 tumor proportion score (TPS) was 60% (Interquartile Range 1-80) for patients with baseline NLR < 5 vs 20% (IQR 0-60) for patients with NLR ≥5, P = 0.037. Conclusions: We confirmed the prognostic value of NLR for patients with advanced NSCLC at baseline and during early treatment in patients with NSCLC receiving first line ICI treatment. We also found an association between elevated NLR and lower PD-L1 expression. Future study with larger cohort is still needed to further delineate these relationships.

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2836
Author(s):  
Kamila Wojas-Krawczyk ◽  
Paweł Krawczyk ◽  
Michał Gil ◽  
Maciej Strzemski

Due to the limited effectiveness of immunotherapy used as first-line monotherapy in patients with non-small-cell lung cancer (NSCLC), the concepts of combining classical immunotherapy based on immune checkpoint antibodies with other treatment methods have been developed. Pembrolizumab and atezolizumab were registered in combination with chemotherapy for the treatment of metastatic NSCLC, while durvalumab found its application in consolidation therapy after successful chemoradiotherapy in patients with locally advanced NSCLC. Exceptionally attractive, due to their relatively low toxicity and high effectiveness, are treatment approaches in which a combination of two different immunotherapy methods is applied. This method is based on observations from clinical trials in which nivolumab and ipilimumab were used as first-line therapy for advanced NSCLC. It turned out that the dual blockade of immune checkpoints activated T lymphocytes in different compartments of the immune response, at the same time affecting the downregulation of immune suppressor cells (regulatory T cells). These experiments not only resulted in the registration of combination therapy with nivolumab and ipilimumab, but also initiated other clinical trials using immune checkpoint inhibitors (ICIs) in combination with other ICIs or activators of costimulatory molecules found on immune cells. There are also studies in which ICIs are associated with molecules that modify the tumour environment. This paper describes the mechanism of the synergistic effect of a combination of different immunotherapy methods in NSCLC patients.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2658
Author(s):  
Jin-Yuan Shih ◽  
Akira Inoue ◽  
Rebecca Cheng ◽  
Rocio Varea ◽  
Sang-We Kim

Pemetrexed is currently mainly considered for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) negative for gene mutations/rearrangements (wild-type disease (WTD)). This narrative review aimed to highlight the role of pemetrexed in the treatment of onco-driven nonsquamous advanced NSCLC by reviewing published clinical studies. For epidermal growth factor receptor (EGFR) mutations, patient survival following first-line pemetrexed–platinum was longer than for WTD. Later-line pemetrexed-based treatment after tyrosine kinase inhibitor (TKI) failure provided greater benefits than non-pemetrexed regimens. First- and later-line pemetrexed-based therapy also provided survival benefits in patients with anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangements. In patients with rearranged during transfection (RET) proto-oncogene rearrangements, survival with pemetrexed was similar to that in ALK- and ROS1-positive patients and longer than that in patients with Kirsten rat sarcoma (KRAS) virus proto-oncogene mutations or WTD, although the available studies were limited. For Erb-b2 receptor tyrosine kinase 2 (ERRB2) mutations, first-line pemetrexed showed outcomes similar to those for EGFR and KRAS alterations. Data on pemetrexed in patients with KRAS mutations or MNNG HOS-transforming (MET) expression were limited. Pemetrexed could be an option for first- and second-line treatment for TKI failure in nonsquamous advanced NSCLC with select targetable driver mutations.


2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 284-284
Author(s):  
Elizabeth B. Lamont ◽  
Nancy Lynn Keating ◽  
Christopher G. Azzoli ◽  
Mary Beth Landrum

284 Background: There is some evidence that cisplatin-based chemotherapy doublet regimens are more efficacious than the less toxic carboplatin-based doublet regimens for advanced non-small cell lung cancer (NSCLC) but little evidence of effectiveness in elderly cancer patients treated in the usual care setting. We estimated differences in survival and post-treatment morbidity between first-line cisplatin-based and carboplatin-based doublet regimens in elderly Medicare patients with advanced NSCLC. Methods: We identified 13,406 elderly Medicare patients who were diagnosed with stage IV NSCLC between 1995-2009 in SEER regions and treated with either a cisplatin-based doublet chemotherapy regimen or a carboplatin-based doublet chemotherapy regimen in the subsequent six months. Using propensity score weighting, we balanced the two treatment cohorts with respect to observable attributes. We then estimated survival and toxicity according to treatment. Results: Overall patients treated with cisplatin-based doublets lived nearly two weeks longer on average than patients treated with carboplatin-based doublets (i.e., 7.4 months vs. 7.0 months, p=0.05) survival differences were not appreciated in subsets of patients with adenocarcinoma or squamous carcinoma. Patients treated with cisplatin-based doublets were slightly more likely than those patients treated with carboplatin-based doublets to be hospitalized (i.e., 42.9% vs 39.8%, p<0.01) and use intensive hospital-based care. Conclusions: Among elderly Medicare patients with advanced NSCLC, those treated with first line cisplatin-based doublet chemotherapy regimens lived slightly longer than those treated with carboplatin-based doublet regimens, but also utilized more hospital-based care following treatment. The difference in overall survival is not clinically significant, and does not appear to justify the added toxicity.


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