scholarly journals Two Complementarity Immunotherapeutics in Non-Small-Cell Lung Cancer Patients—Mechanism of Action and Future Concepts

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2836
Author(s):  
Kamila Wojas-Krawczyk ◽  
Paweł Krawczyk ◽  
Michał Gil ◽  
Maciej Strzemski
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Limited Effectiveness

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.

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 ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Prognostic Value ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Lymphocyte Ratio

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.

scholarly journals Are clinical trial eligibility criteria an accurate reflection of a real-world population of advanced non-small-cell lung cancer patients?

2018 ◽  
Vol 25 (4) ◽  
Author(s):  
K. Al-Baimani ◽  
H. Jonker ◽  
T. Zhang ◽  
G.D. Goss ◽  
S.A. Laurie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Eligibility Criteria ◽  
Ecog Ps

Background Advanced non-small-cell lung cancer (nsclc) represents a major health issue globally. Systemic treatment decisions are informed by clinical trials, which, over years, have improved the survival of patients with advanced nsclc. The applicability of clinical trial results to the broad lung cancer population is unclear because strict eligibility criteria in trials generally select for optimal patients.Methods We performed a retrospective chart review of all consecutive patients with advanced nsclc seen in outpatient consultation at our academic institution between September 2009 and September 2012, collecting data about patient demographics and cancer characteristics, treatment, and survival from hospital and pharmacy records. Two sets of arbitrary trial eligibility criteria were applied to the cohort. Scenario A stipulated Eastern Cooperative Oncology Group performance status (ecog ps) 0–1, no brain metastasis, creatinine less than 120 μmol/L, and no second malignancy. Less-strict scenario B stipulated ecog ps 0–2 and creatinine less than 120 μmol/L. We then used the two scenarios to analyze treatment and survival of patients by trial eligibility status.Results The 528 included patients had a median age of 67 years, with 55% being men and 58% having adenocarcinoma. Of those 528 patients, 291 received at least 1 line of palliative systemic therapy. Using the scenario A eligibility criteria, 73% were trial-ineligible. However, 46% of “ineligible” patients actually received therapy and experienced survival similar to that of the “eligible” treated patients (10.2 months vs. 11.6 months, p = 0.10). Using the scenario B criteria, only 35% were ineligible, but again, the survival of treated patients was similar in the ineligible and eligible groups (10.1 months vs. 10.9 months, p = 0.57).Conclusions Current trial eligibility criteria are often strict and limit the enrolment of patients in clinical trials. Our results suggest that, depending on the chosen drug, its toxicities and tolerability, eligibility criteria could be carefully reviewed and relaxed.

scholarly journals Does Pemetrexed Work in Targetable, Nonsquamous Non-Small-Cell Lung Cancer? A Narrative Review

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2658
Author(s):  
Jin-Yuan Shih ◽  
Akira Inoue ◽  
Rebecca Cheng ◽  
Rocio Varea ◽  
Sang-We Kim
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Narrative Review ◽  
Small Cell Lung ◽  
First Line ◽  
Anaplastic Lymphoma

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.

scholarly journals First line Immunotherapy for Non-Small Cell Lung Cancer

2020 ◽  
Vol 13 (11) ◽  
pp. 373
Author(s):  
Nicola J. Nasser ◽  
Miguel Gorenberg ◽  
Abed Agbarya
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Phase 3 ◽  
Programmed Death

Immunotherapy for non-small cell lung cancer (NSCLC) is incorporated increasingly in first line treatments protocols. Multiple phase 3 studies have tested different medications targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), with or without chemotherapy. The inclusion criteria differ between the various clinical trials, including the cut-off levels of PD-L1 expression on tumor cells, and the tumor histology (squamous or non-squamous). Patients with tumor expression levels of PD-L1 ≥ 50% are candidates for treatment with single agent Pembrolizumab or Atezolizumab. Patients with PD-L1 < 50% are candidates for immunotherapy with pembrolizumab as a single agent if PL-1 > 1%; immunotherapy doublet, Nivolumab and Ipilimumab, or single agent immunotherapy combined with chemotherapy. Here we review phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.

Effectiveness of cisplatin versus carboplatin-based doublet chemotherapy in elderly Medicare patients with advanced non-small cell lung cancer.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 284-284
Author(s):  
Elizabeth B. Lamont ◽  
Nancy Lynn Keating ◽  
Christopher G. Azzoli ◽  
Mary Beth Landrum
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Chemotherapy Regimen ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Medicare Patients ◽  
Doublet Chemotherapy

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.

scholarly journals The landscape of immune checkpoint inhibitor therapy in advanced lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengdi Wang ◽  
Jingwei Li ◽  
Qiran Zhang ◽  
Jiayang Wu ◽  
Yuxuan Xiao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Treatment

Abstract Background The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types. Methods We identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings. Results Overall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70–0.79] and [HR = 0.82; 95% CI, 0.75–0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC. Conclusion ICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

scholarly journals Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab for Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaomin Wan ◽  
Xiaohui Zeng ◽  
Liubao Peng ◽  
Ye Peng ◽  
Qiao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Subgroup Analyses ◽  
The Cost

Objective: This study evaluated the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line setting for patients with advanced non-small-cell lung cancer (NSCLC) from the US payer perspective.Materials and methods: A Markov model wasdeveloped to evaluate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line treatment of advanced NSCLC. The survival benefits of nivolumab plus ipilimumab were based on the results of the CheckMate 227 trial. The main endpoints of the model were cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Univariable and probabilistic sensitivity analyses were conducted to assess model uncertainty. Additonal subgroup analyses were also performed.Results: nivolumab plus ipilimumab produced a gain of 0.62 QALYs, at a cost of $104238 per QALY. The variables that had the greatest influence on the ICER were body weight and overall survival (OS) hazard ratio (HR). The probability of nivolumab plus ipilimumab being cost-effectiveness compared to chemotherapy is 50.7 and 66.2% when the willingness-to-pay (WTP) value is $ 100,000 and $ 150,000 per QALY. The results of subgroup analyses showed the ICER remained below $150,000/QALY regardless of the PD-L1 expression level.Conclusions: nivolumab plus ipilimumab was estimated to be cost-effective compared with chemotherapy for patients with advanced NSCLC at a WTP threshold from 100,000/QALY to 150,000/QALY.

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