14 results on '"Crizotinib adverse effects"'
Search Results
2. Efficacy and Safety of Brigatinib Compared With Crizotinib in Asian vs. Non-Asian Patients With Locally Advanced or Metastatic ALK-Inhibitor-Naive ALK+ Non-Small Cell Lung Cancer: Final Results From the Phase III ALTA-1L Study.
- Author
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Ahn MJ, Kim HR, Yang JCH, Han JY, Li JY, Hochmair MJ, Chang GC, Delmonte A, Lee KH, Campelo RG, Gridelli C, Spira AI, Califano R, Griesinger F, Ghosh S, Felip E, Kim DW, Liu Y, Zhang P, Popat S, and Camidge DR
- Subjects
- Humans, Crizotinib adverse effects, Protein Kinase Inhibitors therapeutic use, Asian People, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung ethnology, Lung Neoplasms drug therapy, Lung Neoplasms ethnology, Lung Neoplasms pathology
- Abstract
Background: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor with demonstrated efficacy in locally advanced and metastatic non-small cell lung cancer (NSCLC) in crizotinib-refractory and ALK inhibitor-naive settings. This analysis assessed brigatinib in Asian vs. non-Asian patients from the first-line ALTA-1L trial., Patients and Methods: This was a subgroup analysis from the phase III ALTA-1L trial of brigatinib vs. crizotinib in ALK inhibitor-naive ALK+ NSCLC. The primary endpoint was progression-free survival (PFS) as assessed by blinded independent review committee (BIRC). Secondary endpoints included confirmed objective response rate (ORR) and overall survival (OS) in the overall population and BIRC-assessed intracranial ORR and PFS in patients with brain metastases., Results: Of the 275 randomized patients, 108 were Asian. Brigatinib showed consistent superiority in BIRC-assessed PFS vs. crizotinib in Asian (hazard ratio [HR]: 0.35 [95% CI: 0.20-0.59]; log-rank P = .0001; median 24.0 vs. 11.1 months) and non-Asian (HR: 0.56 [95% CI: 0.38-0.84]; log-rank P = .0041; median 24.7 vs. 9.4 months) patients. Results were consistent with investigator-assessed PFS and BIRC-assessed intracranial PFS. Brigatinib was well tolerated. Toxicity profiles and dose modification rates were similar between Asian and non-Asian patients., Conclusion: Efficacy with brigatinib was consistently better than with crizotinib in Asian and non-Asian patients with locally advanced or metastatic ALK inhibitor-naive ALK-+ NSCLC. There were no clinically notable differences in overall safety in Asian vs. non-Asian patients., (Copyright © 2022. Published by Elsevier Inc.)
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- 2022
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3. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial.
- Author
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Pal SK, Tangen C, Thompson IM Jr, Balzer-Haas N, George DJ, Heng DYC, Shuch B, Stein M, Tretiakova M, Humphrey P, Adeniran A, Narayan V, Bjarnason GA, Vaishampayan U, Alva A, Zhang T, Cole S, Plets M, Wright J, and Lara PN Jr
- Subjects
- Aged, Anilides adverse effects, Canada, Carcinoma, Renal Cell mortality, Crizotinib administration & dosage, Crizotinib adverse effects, Female, Humans, Kidney Neoplasms mortality, Male, Middle Aged, Progression-Free Survival, Protein Kinase Inhibitors adverse effects, Proto-Oncogene Proteins c-met drug effects, Pyrazines administration & dosage, Pyrazines adverse effects, Pyridines adverse effects, Sunitinib adverse effects, Triazines administration & dosage, Triazines adverse effects, United States, Anilides administration & dosage, Carcinoma, Renal Cell drug therapy, Kidney Neoplasms drug therapy, Protein Kinase Inhibitors administration & dosage, Pyridines administration & dosage, Sunitinib administration & dosage
- Abstract
Background: MET (also known as hepatocyte growth factor receptor) signalling is a key driver of papillary renal cell carcinoma (PRCC). Given that no optimal therapy for metastatic PRCC exists, we aimed to compare an existing standard of care, sunitinib, with the MET kinase inhibitors cabozantinib, crizotinib, and savolitinib for treatment of patients with PRCC., Methods: We did a randomised, open-label, phase 2 trial done in 65 centres in the USA and Canada. Eligible patients were aged 18 years or older with metastatic PRCC who had received up to one previous therapy (excluding vascular endothelial growth factor-directed and MET-directed agents). Patients were randomly assigned to receive sunitinib, cabozantinib, crizotinib, or savolitinib, with stratification by receipt of previous therapy and PRCC subtype. All drug doses were administered orally: sunitinib 50 mg, 4 weeks on and 2 weeks off (dose reductions to 37·5 mg and 25 mg allowed); cabozantinib 60 mg daily (reductions to 40 mg and 20 mg allowed); crizotinib 250 mg twice daily (reductions to 200 mg twice daily and 250 mg once daily allowed); and savolitinib 600 mg daily (reductions to 400 mg and 200 mg allowed). Progression-free survival (PFS) was the primary endpoint. Analyses were done in an intention-to-treat population, with patients who did not receive protocol therapy excluded from safety analyses. This trial is registered with ClinicalTrials.gov, NCT02761057., Findings: Between April 5, 2016, and Dec 15, 2019, 152 patients were randomly assigned to one of four study groups. Five patients were identified as ineligible post-randomisation and were excluded from these analyses, resulting in 147 eligible patients. Assignment to the savolitinib (29 patients) and crizotinib (28 patients) groups was halted after a prespecified futility analysis; planned accrual was completed for both sunitinib (46 patients) and cabozantinib (44 patients) groups. PFS was longer in patients in the cabozantinib group (median 9·0 months, 95% CI 6-12) than in the sunitinib group (5·6 months, 3-7; hazard ratio for progression or death 0·60, 0·37-0·97, one-sided p=0·019). Response rate for cabozantinib was 23% versus 4% for sunitinib (two-sided p=0·010). Savolitinib and crizotinib did not improve PFS compared with sunitinib. Grade 3 or 4 adverse events occurred in 31 (69%) of 45 patients receiving sunitinib, 32 (74%) of 43 receiving cabozantinib, ten (37%) of 27 receiving crizotinib, and 11 (39%) of 28 receiving savolitinib; one grade 5 thromboembolic event was recorded in the cabozantinib group., Interpretation: Cabozantinib treatment resulted in significantly longer PFS compared with sunitinib in patients with metastatic PRCC., Funding: National Institutes of Health and National Cancer Institute., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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4. Complex renal cysts combined with hemorrhage during crizotinib treatment for ALK-rearranged lung adenocarcinoma.
- Author
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Yang L, Gu J, and Niu X
- Subjects
- Adenocarcinoma genetics, Anaplastic Lymphoma Kinase genetics, Female, Hemorrhage diagnostic imaging, Humans, Kidney Diseases, Cystic diagnostic imaging, Lung Neoplasms genetics, Magnetic Resonance Imaging, Middle Aged, Ultrasonography, Adenocarcinoma drug therapy, Antineoplastic Agents adverse effects, Crizotinib adverse effects, Hemorrhage chemically induced, Kidney Diseases, Cystic chemically induced, Lung Neoplasms drug therapy
- Abstract
The oral small-molecule tyrosine kinase inhibitor (TKI), crizotinib has been approved as a first-generation anaplastic lymphoma kinase (ALK) inhibitor in treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). Recently, development of complex renal cysts has been reported with crizotinib usage, highlighting the importance of accurate differentiation between complex renal cysts and new metastasis in NSCLC. Here we describe a case study with confirmed EGFR wild-type and ALK-rearranged lung adenocarcinoma who developed complex renal cysts combined with hemorrhage during crizotinib treatment, with no abnormal clinical symptoms or kidney functions observed. Interestingly, without crizotinib treatment termination or reduction, the complex hemorrhagic renal cysts regressed with self-limiting and healing. The combined usage of ultrasound, CT and MRI techniques in the presented case allowed proper monitoring of the internal changes within complex renal cysts. The patient provided written informed consent authorizing publication of clinical case. Thus, better understanding of the imaging features of crizotinib-related renal cysts combined with hemorrhage would avoid misdiagnoses as a new metastatic renal mass or the aggravation of the primary disease, therefore avoiding further invasive investigation., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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5. Revisiting a lower starting dose of alectinib in ALK-Positive non-small cell lung cancer.
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Sacdalan DB and Lucero JA
- Subjects
- Anaplastic Lymphoma Kinase antagonists & inhibitors, Carbazoles adverse effects, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung mortality, Crizotinib administration & dosage, Crizotinib adverse effects, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans, Lung Neoplasms genetics, Lung Neoplasms mortality, Lung Neoplasms pathology, Piperidines adverse effects, Progression-Free Survival, Protein Kinase Inhibitors adverse effects, Randomized Controlled Trials as Topic, Anaplastic Lymphoma Kinase genetics, Carbazoles administration & dosage, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Piperidines administration & dosage, Protein Kinase Inhibitors administration & dosage
- Abstract
We present here a case of ALK-positive lung adenocarcinoma that has been started on Alectinib. Treatment has been initiated at the recommended initial dose, but it subsequently required a dose adjustment following adverse drug events. Alectinib is a second-generation, CNS-active, tyrosine kinase inhibitor used in the treatment of ALK-positive non-small cell lung cancer. Its efficacy as a first-line treatment and as a second-line agent after Crizotinib has been proven across several trials both in terms of overall response rate and progression-free survival. The use of Alectinib is associated with side effects that occasionally lead to treatment discontinuation, interruption, or dose adjustment. Several studies have used two starting doses - 300 mg and 600 mg twice daily - across different populations and have consistently shown efficacy of Alectinib for both treatment doses. Results of these studies have also revealed that body weight, rather than race, affect the pharmacokinetics of Alectinib. Randomized trials have shown that the 600 mg dose is associated with more grade ≥3 adverse events and more changes in treatment in contrast to the 300 mg dose. A lower dose of Alectinib may limit treatment disruptions and dose reductions particularly for specific patient populations-particularly those with a lower body weight., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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6. ROS1-rearranged Non-small-cell Lung Cancer is Associated With a High Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective, Multicenter, Two-arms Trial (METROS).
- Author
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Chiari R, Ricciuti B, Landi L, Morelli AM, Delmonte A, Spitaleri G, Cortinovis DL, Lamberti G, Facchinetti F, Pilotto S, Verusio C, Chella A, Bonanno L, Galetta D, and Cappuzzo F
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Crizotinib therapeutic use, Disease-Free Survival, Female, Gene Rearrangement, Humans, Lung Neoplasms genetics, Lung Neoplasms pathology, Male, Middle Aged, Prognosis, Prospective Studies, Protein Kinase Inhibitors therapeutic use, Risk Factors, Venous Thromboembolism chemically induced, Venous Thromboembolism genetics, Young Adult, Carcinoma, Non-Small-Cell Lung drug therapy, Crizotinib adverse effects, Lung Neoplasms drug therapy, Protein Kinase Inhibitors adverse effects, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins genetics, Venous Thromboembolism pathology
- Abstract
Background: Patients with cancer are at increased risk for venous thromboembolism (VTE), and 8% to 15% of patients with advanced non-small-cell lung cancer (NSCLC) experience a VTE event during the course of their disease. The incidence of VTE in molecularly defined NSCLC subgroups is still unclear. In this study, we investigated the incidence and the clinical correlates of VTE in patients with ROS1-rearranged NSCLC enrolled in the METROS trial (NCT02499614)., Patients and Methods: The METROS trial is a prospective phase II study designed to assess efficacy, safety, and tolerability of crizotinib in patients with pre-treated metastatic NSCLC ROS1 rearrangement (cohort A) or with MET amplification or MET exon 14 mutation (cohort B). Patients with ROS1-rearranged NSCLC enrolled within cohort A and the expansion cohort of the trial were included in the primary analysis., Results: Among 48 patients with ROS1-rearranged NSCLC enrolled in the METROS study, 20 (41.6%) of 48 had at least 1 VTE event. Among them, 7 (35%) of 20 patients had ≥ 2 VTE events. VTE events consisted of pulmonary embolism (46.4%), deep vein thrombosis (39.2%), renal vein thrombosis (7.1%), internal jugular thrombosis (3.5%), and peripheral inserted central catheter-related thrombosis (3.5%). VTE events occurred at disease progression in 35.7% of cases, at diagnosis in 32.1% of cases, and during chemotherapy or crizotinib in 17.8% and 14.2%, respectively., Conclusion: The incidence of VTE is 3- to 5-fold higher in patients harboring ROS1-rearrangment than previously observed for the general population with NSCLC. Larger studies are warranted to confirm our findings and determine whether the molecular profile of NSCLC should be incorporated into a risk-stratification tool and decision-making algorithm for VTE diagnosis and prophylaxis., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
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7. Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.
- Author
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Moro-Sibilot D, Cozic N, Pérol M, Mazières J, Otto J, Souquet PJ, Bahleda R, Wislez M, Zalcman G, Guibert SD, Barlési F, Mennecier B, Monnet I, Sabatier R, Bota S, Dubos C, Verriele V, Haddad V, Ferretti G, Cortot A, De Fraipont F, Jimenez M, Hoog-Labouret N, and Vassal G
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Crizotinib adverse effects, Disease-Free Survival, Female, Gene Rearrangement genetics, Humans, Male, Middle Aged, Molecular Targeted Therapy, Mutation genetics, Oncogene Proteins, Fusion genetics, Progression-Free Survival, Protein Kinase Inhibitors administration & dosage, Carcinoma, Non-Small-Cell Lung drug therapy, Crizotinib administration & dosage, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins c-met genetics
- Abstract
Background: In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC)., Patients and Methods: Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance., Results: From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported., Conclusions: Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified., Clinical Trial Number: NCT02034981., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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8. Development of Complex Renal Cysts during Crizotinib Treatment and Also during Alectinib Treatment: A Possible Drug Class Effect?
- Author
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Longo V, Catino AM, Montrone M, Pesola F, Pizzutilo P, Delbene G, Gatti P, Ferrante A, and Galetta D
- Subjects
- Humans, Kidney Diseases, Cystic pathology, Antineoplastic Agents adverse effects, Carbazoles adverse effects, Crizotinib adverse effects, Kidney Diseases, Cystic chemically induced, Piperidines adverse effects
- Published
- 2019
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9. Interstitial Lung Disease Onset and Its Risk Factors in Japanese Patients With ALK-Positive NSCLC After Treatment With Crizotinib.
- Author
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Gemma A, Kusumoto M, Kurihara Y, Masuda N, Banno S, Endo Y, Houzawa H, Ueno N, Ohki E, and Yoshimura A
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- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Agents pharmacology, Carcinoma, Non-Small-Cell Lung pathology, Child, Child, Preschool, Crizotinib pharmacology, Female, Humans, Japan, Lung Diseases, Interstitial pathology, Lung Neoplasms pathology, Male, Middle Aged, Risk Factors, Young Adult, Antineoplastic Agents adverse effects, Carcinoma, Non-Small-Cell Lung chemically induced, Crizotinib adverse effects, Lung Diseases, Interstitial chemically induced, Lung Neoplasms chemically induced
- Abstract
Introduction: The study objective was to determine the incidence and characteristics of drug-induced interstitial lung disease (ILD) associated with an orally available small-molecule tyrosine kinase inhibitor, crizotinib, in a real-world clinical setting., Methods: Post-marketing surveillance was performed in Japan to obtain information on the safety and efficacy of crizotinib. Target patients included all patients with anaplastic lymphoma kinase-positive NSCLC who received crizotinib during the enrollment period between May 2012 and December 2014. The observation period was 52 weeks. Expert analysis of the ILD incidence was performed by an ILD independent review committee composed of five medical specialists., Results: The safety analysis set included 2028 patients, and more than half of the patients (56.4%) were nonsmokers. The incidence of ILD associated with crizotinib therapy was 5.77%; and 3.45% patients showed grade 3 or greater. Pulmonary edema-like shadows with or without diffuse alveolar damage pattern were observed in crizotinib-associated ILD (incidence: 0.39%), but a causal relationship with the prognosis could not be identified. ILD developed within 4 weeks from initiation of crizotinib administration in 41.9% and within 8 weeks in 69.2% of the patients. Age 55 years or older, Eastern Cooperative Oncology Group performance status 2-4, smoking history, previous or concomitant ILD, and comorbid pleural effusion were statistically determined as significant risk factors for crizotinib-induced ILD., Conclusions: Crizotinib therapy should be applied to the NSCLC patients with any of above risk factors under a cautious monitoring for ILD occurrence, and clinicians should pay attention to the risks of severe ILD., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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10. Severe Acute Hepatitis in a Patient Receiving Alectinib for ALK-Positive Non-Small-Cell Lung Cancer: Histologic Analysis.
- Author
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Zhu VW, Lu Y, and Ou SI
- Subjects
- Acute Disease, Adult, Anaplastic Lymphoma Kinase antagonists & inhibitors, Anaplastic Lymphoma Kinase genetics, Antineoplastic Agents adverse effects, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Crizotinib adverse effects, Female, Hepatitis etiology, Humans, Liver drug effects, Lung Neoplasms genetics, Lung Neoplasms pathology, Antineoplastic Agents therapeutic use, Carbazoles therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Crizotinib therapeutic use, Drug-Related Side Effects and Adverse Reactions diagnosis, Hepatitis diagnosis, Liver pathology, Lung Neoplasms drug therapy, Piperidines therapeutic use
- Published
- 2019
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11. Identification of EML4-ALK Rearrangement and MET Exon 14 R988C Mutation in a Patient with High-Grade Neuroendocrine Lung Carcinoma Who Experienced a Lazarus Response to Crizotinib.
- Author
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Ricciuti B, Marcomigni L, Metro G, Bellezza G, Caselli E, Baglivo S, and Chiari R
- Subjects
- Exons, Female, Humans, Lung Neoplasms pathology, Middle Aged, Mutation, Crizotinib adverse effects, Lung Neoplasms complications, Lung Neoplasms genetics, Oncogene Proteins, Fusion metabolism
- Published
- 2018
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12. Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370).
- Author
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Spigel DR, Reynolds C, Waterhouse D, Garon EB, Chandler J, Babu S, Thurmes P, Spira A, Jotte R, Zhu J, Lin WH, and Blumenschein G Jr
- Subjects
- Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase genetics, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Crizotinib administration & dosage, Crizotinib adverse effects, Female, Humans, Lung Neoplasms genetics, Lung Neoplasms pathology, Male, Middle Aged, Nivolumab administration & dosage, Nivolumab adverse effects, Translocation, Genetic, Anaplastic Lymphoma Kinase antagonists & inhibitors, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
Introduction: Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses. Herein we report data from a study assessing nivolumab plus crizotinib in patients with previously untreated advanced ALK translocation-positive NSCLC., Methods: Group E in CheckMate 370 was a single-arm cohort designed to evaluate the safety of first-line nivolumab (240 mg every 2 weeks) plus crizotinib (250 mg twice daily) in patients with ALK translocation-positive NSCLC. The primary endpoint of safety would be met if ≤20% of patients discontinued treatment due to treatment-related adverse events by week 17. Objective response rate was a secondary endpoint. A planned safety review occurred in November 2016; the data cutoff was May 26, 2017., Results: Of the first 13 patients treated with nivolumab plus crizotinib, 5 (38%) developed severe hepatic toxicities leading to the discontinuation of the combination. Of these, two patients died and the presence of severe hepatic toxicities may have contributed to death. Enrollment was closed and combination treatment discontinued due to observed grade ≥3 hepatic toxicities. Five patients (38%) had a partial response., Conclusions: These findings do not support further evaluation of nivolumab 240 mg every 2 weeks plus crizotinib 250 mg twice daily., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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13. Development of Complex Hepatic Cysts Is a Potential Side Effect of Crizotinib.
- Author
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Zaheed M, Bray VJ, Itchins M, Storer P, and Kao S
- Subjects
- Aged, Antineoplastic Agents pharmacology, Crizotinib pharmacology, Cysts pathology, Female, Humans, Liver Diseases pathology, Middle Aged, Antineoplastic Agents adverse effects, Crizotinib adverse effects, Cysts chemically induced, Liver Diseases etiology
- Published
- 2018
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14. Lung Toxicity in Non-Small-Cell Lung Cancer Patients Exposed to ALK Inhibitors: Report of a Peculiar Case and Systematic Review of the Literature.
- Author
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Pellegrino B, Facchinetti F, Bordi P, Silva M, Gnetti L, and Tiseo M
- Subjects
- Adult, Anaplastic Lymphoma Kinase antagonists & inhibitors, Betamethasone administration & dosage, Carcinoma, Non-Small-Cell Lung epidemiology, Carcinoma, Non-Small-Cell Lung mortality, Crizotinib adverse effects, Crizotinib therapeutic use, Drug-Related Side Effects and Adverse Reactions mortality, Female, Humans, Italy epidemiology, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial mortality, Lung Neoplasms epidemiology, Lung Neoplasms etiology, Lung Neoplasms mortality, Organophosphorus Compounds adverse effects, Organophosphorus Compounds therapeutic use, Pneumonia etiology, Pneumonia mortality, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors pharmacology, Pyrimidines adverse effects, Pyrimidines therapeutic use, Survival Analysis, Withholding Treatment statistics & numerical data, Carcinoma, Non-Small-Cell Lung drug therapy, Drug-Related Side Effects and Adverse Reactions epidemiology, Lung Diseases, Interstitial epidemiology, Lung Neoplasms drug therapy, Pneumonia epidemiology, Protein Kinase Inhibitors therapeutic use
- Abstract
Lung toxicity is a potential fatal effect involving non-small-cell lung cancer (NSCLC) patients exposed to tyrosine kinase inhibitors (TKIs). Moving from our experience regarding a patient who developed lung toxicity while receiving 2 different anaplastic lymphoma kinase (ALK)-TKIs, we performed a systematic review to assess the epidemiologic magnitude and the clinical significance of such toxicity in NSCLC patients treated with ALK-TKIs. Studies were identified using MEDLINE and additional sources (European Society for Medical Oncology, American Society of Clinical Oncology, and World Conference on Lung Cancer abstracts) in agreement with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines. Lung toxicity was reported in 105 of 4943 NSCLC patients (2.1%). Crizotinib was responsible for pulmonary adverse events (AEs) in 1.8% of exposed patients (49 of 2706). With the limit of a lower number of treated patients (n = 359), brigatinib resulted as the most frequently involved in lung toxicity (7%; n = 25). Pulmonary AEs during therapy with ceritinib, alectinib, and lorlatinib occurred in 1.1%, 2.6%, and 1.8% of the patients, respectively. Sixty-five percent of cases accounted for Grade 3 or 4 events, with a mortality rate of 9%. Radiological patterns of pneumonia were reported in 25 patients, whereas imaging evocative of interstitial lung disease in 37. Overall, 26 of 105 patients (25%) permanently discontinued treatment because of lung toxicity. Lung toxicity is a rare albeit potentially severe side effect in NSCLC patients receiving ALK-TKIs, apparently more frequent with brigatinib. Its early recognition and treatment are crucial for the best outcome of this subgroup of patients, whose overall prognosis is being improved by the availability of several targeted agents., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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