Treatment of ALK-Positive Non–Small Cell Lung Cancer

2012 ◽  
Vol 136 (10) ◽  
pp. 1201-1204 ◽  
Author(s):  
Yung-Jue Bang
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
Free Survival ◽  
Alk Positive

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.

Efficacy and safety of crizotinib in patients with anaplastic lymphoma kinase-positive stage IV non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20516-e20516 ◽  
Author(s):  
Ahmed M. Mohi El.Din ◽  
Ayman Ahamd Rasmy
Keyword(s):  
Lung Cancer ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
Free Survival ◽  
Anaplastic Lymphoma ◽  
Alk Positive

e20516 Background: Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting ALK, MET, and ROS1 tyrosine kinases. It was first approved by the Food and Drug Administration (FDA) in 2011 for treatment of patients in late-stage (locally advanced or metastatic) non-small cell lung cancer (NSCLC) with abnormal anaplastic lymphoma kinase (ALK) gene as detected by an FDA-approved test, as it confers improved progression-free survival comparison with chemotherapy. Methods: This is a retrospective chart review study of patients with stage IV ALK-positive NSCLC who attended the medical oncology department of Kuwait Cancer Control Centre (Kuwait) and King Fahad Specialist Hospital (Saudi Arabia) between January 2013 and May 2016. The efficacy and safety of crizotinib (250 mg orally, twice daily, with or without food.) were evaluated based on overall survival (OS), progression-free survival (PFS), Objective response rate (ORR), time to objective response, duration of response, and dose reduction or cessation because of crizotinib toxicity. Results: Twenty-three patients were involved in this study with a median age of 55.5 years and male-to-female ratio of 2.4:1 The median OS from initiation of crizotinib has not been reached; 1-year overall survival was 71.2%. Crizotinib treatment demonstrated median PFS of 9.6 months (95% CI, 3.0-24.1 months). The ORR was 70.9%. Complete response was achieved in 4.2% of patients, and partial response was achieved in 66.7% of patients. The most frequently reported adverse effects of crizotinib (Grade 1 / 2) were muscle ache, fatigue, nausea, vomiting, diarrhea, constipation, edema, elevated transaminases, bradycardia, and vision disorders. Grade 3 / 4 diarrhea was reported in 12.5% of patients. The proportion of patients who required dose reduction because of Crizotinib-induced bradycardia was 8.3% of patients. Conclusions: Crizotinib appears to be a very favorable option for treating patients with stage IV ALK-positive NSCLC. Crizotinib showed a very tolerable toxicity profile.

Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer

Lung Cancer ◽  
2020 ◽  
Vol 139 ◽  
pp. 195-199 ◽  
Author(s):  
Kazuhiko Nakagawa ◽  
Toyoaki Hida ◽  
Hiroshi Nokihara ◽  
Masahiro Morise ◽  
Koichi Azuma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Alk Positive

scholarly journals Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Farastuk Bozorgmehr ◽  
Adriane Hommertgen ◽  
Johannes Krisam ◽  
Felix Lasitschka ◽  
Jonas Kuon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Palliative Radiotherapy ◽  
Progression Free Survival ◽  
Small Cell ◽  
Photon Radiation ◽  
Small Cell Lung ◽  
Free Survival ◽  
Recist 1.1

Abstract Background Hypofractionated palliative radiotherapy for metastatic lung cancer patients is frequently used in order to ease pain, to increase bone stability, to treat local mass effects, or to prolong progression-free survival at critical sites. Recently introduced, immunotherapy for patients with non-squamous non-small cell lung carcinoma (NSCLC) has significantly improved outcome in this cohort. Preclinical and early clinical data suggest that the combination of photon radiation with programmed death-1 (PD-1) targeting immunotherapies may promote a strong and durable immune response against tumor manifestations both within and beyond radiation targets. Methods/design In the present prospective, two-group, non-randomized, open-label phase II trial, 130 patients with stage IV non-squamous NSCLC in 2nd-line or 3rd-line treatment will be included. 65 patients with a clinical indication for palliative radiotherapy to non-cerebral/non-pulmonary metastatic sites will receive 240 mg nivolumab followed by palliative radiotherapy with 5 × 4 Gray (Gy) = 20 Gy photon radiation, which will be initiated within 72 h after first nivolumab administration (Group A). 65 patients without an indication for radiotherapy will only receive nivolumab (Group B). Nivolumab will be further administered every two weeks in both groups and will be continued until progression and loss of clinical benefit or until occurrence of limiting toxicities. The primary endpoint will be the objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints will be progression-free survival (PFS) according to RECIST 1.1, overall survival, descriptive subgroup analyses according to PD-L1 expression, toxicity and quality of life. Since response patterns following immunotherapies differ from those after conventional cytostatic agents, both objective response rate and progression-free survival will additionally be assessed according to immune-related RECIST (irRECIST) criteria. Discussion The FORCE study will prospectively investigate response rates, progression-free and overall survival (OS), and toxicity of nivolumab with and without hypofractionated palliative radiotherapy in a group of 130 patients with metastatic non-small cell lung cancer (non-squamous histology) in 2nd-line or 3rd-line treatment. This trial will contribute prospective data to the repeatedly published observation that the combination of hypofractionated photon radiotherapy and medical immunotherapy is not only safe but will also promote antitumoral immune responses. Trial registration Clinicaltrials.gov identifier: NCT03044626 (Date of initial registration: 05 January 2017). Eudra-CT Number: 2015–005741-31 (Date of initial registration: 18 December 2015).

Neutrophil to lymphocyte ratio as predictive of prolonged progression free survival (PFS) and overall survival (OS) in patients with metastatic non-small cell lung cancer (NSCLC) treated with second-line PD-1 immune checkpoint inhibitors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14530-e14530 ◽  
Author(s):  
Stephanie Labomascus ◽  
Ibtihaj Fughhi ◽  
Philip Bonomi ◽  
Mary J. Fidler ◽  
Jeffrey Allen Borgia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
Free Survival

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.

Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non–Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study

2012 ◽  
Vol 30 (17) ◽  
pp. 2046-2054 ◽  
Author(s):  
Thomas J. Lynch ◽  
Igor Bondarenko ◽  
Alexander Luft ◽  
Piotr Serwatowski ◽  
Fabrice Barlesi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Who Criteria

Purpose Ipilimumab, which is an anti–cytotoxic T-cell lymphocyte-4 monoclonal antibody, showed a survival benefit in melanoma with adverse events (AEs) managed by protocol-defined guidelines. A phase II study in lung cancer assessed the activity of ipilimumab plus paclitaxel and carboplatin. Patients and Methods Patients (N = 204) with chemotherapy-naive non–small-cell lung cancer (NSCLC) were randomly assigned 1:1:1 to receive paclitaxel (175 mg/m2) and carboplatin (area under the curve, 6) with either placebo (control) or ipilimumab in one of the following two regimens: concurrent ipilimumab (four doses of ipilimumab plus paclitaxel and carboplatin followed by two doses of placebo plus paclitaxel and carboplatin) or phased ipilimumab (two doses of placebo plus paclitaxel and carboplatin followed by four doses of ipilimumab plus paclitaxel and carboplatin).Treatment was administered intravenously every 3 weeks for ≤ 18 weeks (induction). Eligible patients continued ipilimumab or placebo every 12 weeks as maintenance therapy. Response was assessed by using immune-related response criteria and modified WHO criteria. The primary end point was immune-related progression-free survival (irPFS). Other end points were progression-free survival (PFS), best overall response rate (BORR), immune-related BORR (irBORR), overall survival (OS), and safety. Results The study met its primary end point of improved irPFS for phased ipilimumab versus the control (hazard ratio [HR], 0.72; P = .05), but not for concurrent ipilimumab (HR, 0.81; P = .13). Phased ipilimumab also improved PFS according to modified WHO criteria (HR, 0.69; P = .02). Phased ipilimumab, concurrent ipilimumab, and control treatments were associated with a median irPFS of 5.7, 5.5, and 4.6 months, respectively, a median PFS of 5.1, 4.1, and 4.2 months, respectively, an irBORR of 32%, 21% and 18%, respectively, a BORR of 32%, 21% and 14%, respectively, and a median OS of 12.2, 9.7, and 8.3 months. Overall rates of grade 3 and 4 immune-related AEs were 15%, 20%, and 6% for phased ipilimumab, concurrent ipilimumab, and the control, respectively. Two patients (concurrent, one patient; control, one patient) died from treatment-related toxicity. Conclusion Phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS, which supports additional investigation of ipilimumab in NSCLC.

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