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 Cost-effectiveness analysis of ceritinib vs. crizotinib in previously untreated anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in Hong Kong

2020 ◽  
Author(s):  
Herbert Loong ◽  
Carlos K H Wong ◽  
Linda K S Leung ◽  
Catherine P K Chan ◽  
Andrea Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Time Horizon ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Anaplastic Lymphoma ◽  
First Line Treatment

Abstract Introduction: Lower-dose ceritinib (450mg) once-daily with food was approved in 2018 in Hong Kong (HK) for first-line treatment of patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC). This study examined the cost-effectiveness of ceritinib vs. crizotinib in the first-line treatment of ALK+ NSCLC from a HK healthcare service provider's or government's perspective. Methods: Costs and effectiveness of first-line ceritinib vs. crizotinib over a 20-year time horizon was evaluated using a partitioned survival model with three health states (stable disease, progressed disease, and death). The efficacy data for ceritinib were obtained from a phase 3 trial comparing ceritinib with chemotherapy for advanced non-small cell lung cancer (ASCEND-4) and extrapolated using parametric survival models. Long-term survival associated with crizotinib were estimated using hazard ratio of crizotinib vs. ceritinib obtained from matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014 trials. Drug acquisition, administration, adverse events costs, and medical costs associated with each health state were obtained from public sources and converted to 2018 US Dollars. Incremental costs per quality-adjusted-life-year (QALY) and life-year (LY) gained were estimated for ceritinib vs. crizotinib. Results: The base case results showed that ceritinib was associated with 3.22 QALYs, 4.51 LYs, and total costs of $157,581 over 20 years. Patients receiving crizotinib had 2.68 QALYs, 3.85 LYs, and $150,424 total costs over the same time horizon. The incremental cost per QALY gained for ceritinib vs crizotinib was $13,343. Results were robust to deterministic sensitivity analyses in most scenarios. Conclusion: Ceritinib offers a cost-effective option compared to crizotinib for previously untreated ALK+ advanced NCSLC in HK.

scholarly journals Immunotherapy in non-metastatic non-small cell lung cancer: Can the benefits of stage IV therapy be translated into earlier stages?

2018 ◽  
Vol 10 ◽  
pp. 175883591877281 ◽  
Author(s):  
Griet Deslypere ◽  
Dorothée Gullentops ◽  
Els Wauters ◽  
Johan Vansteenkiste
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Stage Iv ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR) activating mutations or anaplastic lymphoma kinase ( ALK) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC. Aside from chemotherapy and targeted therapy, immunotherapy has become the third pillar in the treatment armamentarium of advanced NSCLC. Antigen-specific immunotherapy (cancer vaccination) has been disappointing in large phase III clinical trials in stages I–III NSCLC. Based on the recent breakthroughs with immune checkpoint inhibitor immunotherapy in metastatic NSCLC, much hope currently rests on the use of this approach in patients with stage I–III NSCLC as well. Here we give a brief overview of how most new therapeutic approaches for advanced NSCLC failed in other stages, and then elaborate on the role of immunotherapy in patients with stage I–III NSCLC.

scholarly journals Gefitinib in Non Small Cell Lung Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Raffaele Costanzo ◽  
Maria Carmela Piccirillo ◽  
Claudia Sandomenico ◽  
Guido Carillio ◽  
Agnese Montanino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Line Treatment ◽  
Phase 2 ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Treatment

Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) that plays a key role in the biology of non small cell lung cancer (NSCLC). Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

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.

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 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.

Multidrug Combinations for First-line Therapy of Advanced Non-small-cell Lung Cancer

2011 ◽  
Vol 07 (01) ◽  
pp. 25
Author(s):  
Ha N Tran ◽  
Suresh S Ramalingam ◽  
◽  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Lung cancer is a common disease with a high mortality rate. Non-small-cell lung cancer (NSCLC), which accounts for almost 85% of all cases of lung cancer, is often diagnosed at an advanced stage. Platinum-based two-drug combination regimens have become the standard of care and should be considered in patients with a good performance status (Eastern Cooperative Oncology Group performance status scale 0–1). The addition of a third chemotherapy agent is not recommended, since there is additional toxicity without a definite survival benefit. In recent years, histology has emerged as an important factor in treatment selection. In patients with non-squamous NSCLC, the cisplatin–pemetrexed regimen has demonstrated superiority over cisplatin–gemcitabine and has emerged as a preferred regimen for this subset of patients. The addition of targeted agents such as bevacizumab or cetuximab to platinum doublets has also demonstrated modest improvements in overall survival for firstline therapy of advanced NSCLC. The identification of patient-selection methods for the use of these agents remains a major challenge. Recently, the use of maintenance therapy has emerged as an option for patients who complete the recommended four to six cycles of chemotherapy. This article reviews the various first-line therapy options for advanced NSCLC.

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