Therapeutic efficacy and safety of PCSK9-monoclonal antibodies on familial hypercholesterolemia and statin-intolerant patients: A meta-analysis of 15 randomized controlled trials.

Sci Rep. 2017 03 22;7(1):238

Authors: Qian LJ, Gao Y, Zhang YM, Chu M, Yao J, Xu D

Abstract
Proprotein convertase subtilisin/kexin9 monoclonal antibodies (PCSK9-mAb) have been studied intensively to identify their effect in lowering levels of low density lipoprotein cholesterol (LDL-C). However, the applicable target of PCSK9-mAbs remains inconclusive so far. Therefore, this first meta-analysis was carried out to clarify the therapeutic efficacy and safety of PCSK9-mAbs on the potential patients: familial hypercholesterolemia and statin-intolerant patients. All randomized controlled trials that met the search terms were retrieved in multiple databases. Efficacy outcomes included parameter changes from baseline in LDL-C and other lipid levels. Therapeutic safety were evaluated by rates of common adverse events. A total of 15 studies encompassing 4,288 patients with at least 8 weeks duration were selected. Overall, the therapeutic efficacy was achieved with significant reduction in LDL-C, TC, TG, Lp(a), Apo-B versus placebo. The decline in familial hypercholesterolemia patients (-53.28%, 95% CI: -59.88 to -46.68%) was even more obvious than that in statin-intolerant patients (-34.95%, 95% CI: -41.46 to -28.45%). No obvious safety difference was found out in the rates of common and serious adverse events. To conclude, PCSK9-mAb contributes to the decreased level of LDL-C and other lipids in familial hypercholesterolemia and statin-intolerant patients with satisfactory safety and tolerability.

PMID: 28331223 [PubMed - indexed for MEDLINE]

Remote control of glucose homeostasis in vivo using photopharmacology.

Sci Rep. 2017 03 22;7(1):291

Authors: Mehta ZB, Johnston NR, Nguyen-Tu MS, Broichhagen J, Schultz P, Larner DP, Leclerc I, Trauner D, Rutter GA, Hodson DJ

Abstract
Photopharmacology describes the use of light to precisely deliver drug activity in space and time. Such approaches promise to improve drug specificity by reducing off-target effects. As a proof-of-concept, we have subjected the fourth generation photoswitchable sulfonylurea JB253 to comprehensive toxicology assessment, including mutagenicity and maximum/repeated tolerated dose studies, as well as in vivo testing in rodents. Here, we show that JB253 is well-tolerated with minimal mutagenicity and can be used to optically-control glucose homeostasis in anesthetized mice following delivery of blue light to the pancreas. These studies provide the first demonstration that photopharmacology may one day be applicable to the light-guided treatment of type 2 diabetes and other metabolic disease states in vivo in humans.

PMID: 28331198 [PubMed - indexed for MEDLINE]

[Gastrointestinal tract diseases induced by medications].

Pathologe. 2018 Aug 31;:

Authors: Bläker H

Abstract
Gastrointestinal symptoms are common side effects of medical drugs. They are usually mild but sometimes require diagnostic endoscopy and histologic evaluation. Due to the rapidly increasing number of drugs developed especially for cancer treatment, pathologists are faced with a spectrum of different drug-associated histologies in all segments of the gastrointestinal tract. Some medication-induced mucosal damage features may mimic classical pathologies of nondrug-associated diseases, while others result in novel phenotypes. The present article focusses on the histologic presentations of gastrointestinal diseases induced by medications that either compromise or induce immune response.

PMID: 30171343 [PubMed - as supplied by publisher]

Drug-induced oral lichenoid reaction during nivolumab therapy.

Int J Oral Maxillofac Surg. 2018 Aug 28;:

Authors: Enomoto Y, Nakatani H, Kondo S, Kasai T, Tsuchiya Y

Abstract
Oral lichenoid reaction, an immune-related adverse event of immunotherapy, has been reported in very few patients receiving anti-programmed cell death receptor-1 (anti-PD-1) therapy. Here, we describe a case of severe stomatitis (grade ≥3 by the Common Terminology Criteria for Adverse Events, version 4.0) accompanied by pharyngolaryngitis that was observed in a patient receiving nivolumab therapy. The stomatitis was diagnosed as drug-induced lichenoid reaction. Nivolumab therapy was discontinued, and the patient was administered systemic prednisolone (1mg/kg). Most of the patient's mucosal changes in the oral cavity and pharyngolarynx resolved within approximately 3 weeks after starting the prednisolone. Clinicians should be aware that severe oral lichenoid reactions can occur in patients receiving anti-PD-1 therapy.

PMID: 30170775 [PubMed - as supplied by publisher]

[(Immuno‑)Pathology of drug side effects in the kidney].

Pathologe. 2018 Aug 30;:

Authors: Pfister F, Büttner-Herold M, Amann K

Abstract
Nephrotoxicity or renal side effects of drugs are frequent and may vary in their clinical presentation. Various types of acute and chronic kidney disease are known to develop as a consequence or side effect of a long list of drugs with nephrotoxicity most commonly being associated with injury in the tubulointerstitial compartment. In addition, drug-induced glomerular and vascular disease have also been reported, either as the result of direct cellular injury or immune-mediated injury to glomerular or endothelial cells. From a clinical point of view it is important to recognize such drug-induced nephropathies early in order to prevent or adequately treat them to favour kidney recovery and to avoid long-lasting negative consequences for kidney function.This article will focus on the typical morphology and pathogenesis of some frequent drug-induced renal diseases.

PMID: 30167781 [PubMed - as supplied by publisher]

Ovarian effects of radiation and cytotoxic chemotherapy damage.

Best Pract Res Clin Obstet Gynaecol. 2018 Jul 26;:

Authors: Cosgrove CM, Salani R

Abstract
Oncologic therapy including chemotherapy and radiation can have a significant impact on ovarian function for young women and girls. Poor health outcomes and loss of fertility are major considerations. The effect of radiation and chemotherapy on ovarian function varies depending on patient age, therapy type and dosage, and cancer type. Surgical and medical interventions are available to reduce the morbidity of premature ovarian failure associated with cancer-directed therapy. Fertility preservation is an important consideration, and several options are available for it; therefore, early consultation with a reproductive or oncofertility specialist is an essential part of oncologic care in young women or girls. This chapter will focus on the effects of radiation and chemotherapy on ovarian function and strategies to improve the reproductive care in women with cancer.

PMID: 30166215 [PubMed - as supplied by publisher]

Side effects of addiction treatment.

Science. 2018 08 24;361(6404):761

Authors: Tang GY, Parekh J

PMID: 30139864 [PubMed - indexed for MEDLINE]

Review of antimicrobial use and considerations in the elderly population.

Clin Interv Aging. 2018;13:657-667

Authors: Giarratano A, Green SE, Nicolau DP

Abstract
Pharmacologic management of infections in elderly patients presents multiple challenges to health care professionals due to variable pharmacokinetics, pharmacodynamics, and immune function. Age is a well-established risk factor for infection, but furthermore is a risk factor for prolonged length of hospital stay, increased incidence of complications, and significant and sustained decline in baseline functional status. In 2014, 46.2 million Americans were aged ≥65 years, accounting for 14.5% of the total population. By 2033, for the first time, the population of persons aged ≥65 years is projected to outnumber the people <18 years of age. According to the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, 154 million prescriptions for antimicrobials were estimated to have been written in doctors' offices and emergency departments during a 1-year time period. In 2014, 266.1 million courses of antimicrobials were dispensed to outpatients by US community pharmacies. A study that evaluated 2007-2009 Medicare Part D data found that patients aged ≥65 years used more antimicrobials, at 1.10 per person per year, compared to 0.88 antimicrobials used per person per year in patients aged 0-64 years. With the abundance of antimicrobial prescriptions and the current growth in the number and proportion of older adults in the US, it is essential that health care providers understand appropriate antimicrobial pharmacotherapy in the elderly patient. This review focuses on the use and implications of antimicrobial agents in the elderly population.

PMID: 29713150 [PubMed - indexed for MEDLINE]

Microbiota-drug interactions: Impact on metabolism and efficacy of therapeutics.

Maturitas. 2018 Jun;112:53-63

Authors: Wilkinson EM, Ilhan ZE, Herbst-Kralovetz MM

Abstract
The microbiome not only represents a vital modifier of health and disease, but is a clinically important drug target. Therefore, study of the impact of the human microbiome on drug metabolism, toxicity and efficacy is urgently needed. This review focuses on gut and vaginal microbiomes, and the effect of those microbiomes or components thereof on the pharmacokinetics of specific chemotherapeutic agents, immunotherapies, anti-inflammatory and antimicrobial drugs. In some cases, the presence of specific bacterial species within the microbiome can alter the metabolism of certain drugs, such as chemotherapeutic agents and antiviral drugs. These microbiota-drug interactions are identified mostly through studies using germ-free or microbiome-depleted animal models, or by the administration of specific bacterial isolates. The biotransformation of drugs can cause drug-related toxicities; however, biotransformation also provides a mechanism by which drug developers could exploit host microbiota to create more site-specific drugs. Within this review we consider the importance of the route of drug administration and interactions with microbiota at various mucosal sites. Notably, we discuss the potential utility of bacterial therapeutics in altering the microbiome to enhance therapeutic efficacy and clinical outcomes in a personalized fashion. Based on the data to date, there is a clinically important relationship between microbiota and drug metabolism throughout the lifespan; therefore, profiling of the human microbiome will be essential in order to understand the mechanisms by which these microbiota-drug interactions occur and the degree to which this complex interplay affects drug efficacy.

PMID: 29704918 [PubMed - indexed for MEDLINE]

Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated Review on the Risks Associated with Anticancer Targeted Therapy or Immunotherapies.

J Immunol Res. 2018;2018:5376476

Authors: Ng CY, Chen CB, Wu MY, Wu J, Yang CH, Hui RC, Chang YC, Lu CW

Abstract
Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite). Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.

PMID: 29577050 [PubMed - indexed for MEDLINE]

Automated Screening of Emergency Department Notes for Drug-Associated Bleeding Adverse Events Occurring in Older Adults.

Appl Clin Inform. 2017 10;8(4):1022-1030

Authors: Boyce RD, Jao J, Miller T, Kane-Gill SL

Abstract
Objective To conduct research to show the value of text mining for automatically identifying suspected bleeding adverse drug events (ADEs) in the emergency department (ED). Methods A corpus of ED admission notes was manually annotated for bleeding ADEs. The notes were taken for patients ≥ 65 years of age who had an ICD-9 code for bleeding, the presence of hemoglobin value ≤ 8 g/dL, or were transfused > 2 units of packed red blood cells. This training corpus was used to develop bleeding ADE algorithms using Random Forest and Classification and Regression Tree (CART). A completely separate set of notes was annotated and used to test the classification performance of the final models using the area under the ROC curve (AUROC). Results The best performing CART resulted in an AUROC on the training set of 0.882. The model's AUROC on the test set was 0.827. At a sensitivity of 0.679, the model had a specificity of 0.908 and a positive predictive value (PPV) of 0.814. It had a relatively simple and intuitive structure consisting of 13 decision nodes and 14 leaf nodes. Decision path probabilities ranged from 0.041 to 1.0. The AUROC for the best performing Random Forest method on the training set was 0.917. On the test set, the model's AUROC was 0.859. At a sensitivity of 0.274, the model had a specificity of 0.986 and a PPV of 0.92. Conclusion Both models accurately identify bleeding ADEs using the presence or absence of certain clinical concepts in ED admission notes for older adult patients. The CART model is particularly noteworthy because it does not require significant technical overhead to implement. Future work should seek to replicate the results on a larger test set pulled from another institution.

PMID: 29241242 [PubMed - indexed for MEDLINE]

Effect of prescription medications on erectile dysfunction.

Postgrad Med J. 2018 Mar;94(1109):171-178

Authors: Razdan S, Greer AB, Patel A, Alameddine M, Jue JS, Ramasamy R

Abstract
Erectile dysfunction (ED) affects about 50% of men in the USA and is primarily attributed to physiological (organic) and psychological causes. However, a substantial portion of men suffer from ED due to iatrogenic causes. Common medications such as antihypertensives, non-steroidal anti-inflammatory drugs and antacids may cause ED. Physicians should be aware of the various prescription medications that may cause ED to properly screen and counsel patients on an issue that many may feel too uncomfortable to discuss. In this review, we discuss the physiology, data and alternative therapies for the ED caused by medications.

PMID: 29103015 [PubMed - indexed for MEDLINE]

Chemical toxicity prediction for major classes of industrial chemicals: Is it possible to develop universal models covering cosmetics, drugs, and pesticides?

Food Chem Toxicol. 2018 Feb;112:526-534

Authors: Alves VM, Muratov EN, Zakharov A, Muratov NN, Andrade CH, Tropsha A

Abstract
Computational models have earned broad acceptance for assessing chemical toxicity during early stages of drug discovery or environmental safety assessment. The majority of publicly available QSAR toxicity models have been developed for datasets including mostly drugs or drug-like compounds. We have evaluated and compared chemical spaces occupied by cosmetics, drugs, and pesticides, and explored whether current computational models of toxicity endpoints can be universally applied to all these chemicals. Our analysis of the chemical space overlap and applicability domain (AD) of models built previously for twenty different toxicity endpoints showed that most of these models afforded high coverage (>90%) for all three classes of compounds analyzed herein. Only T. pyriformis models demonstrated lower coverage for drugs and pesticides (38% and 54%, respectively). These results show that, for the most part, historical QSAR models built with data available for different toxicity endpoints can be used for toxicity assessment of novel chemicals irrespective of the intended commercial use; however, the AD restriction is necessary to assure the expected prediction accuracy. Local models may need to be developed to capture chemicals that appear as outliers with respect to global models.

PMID: 28412406 [PubMed - indexed for MEDLINE]

For drug-induced carcinogenesis, the observations are the hypothesis: Invited editorial for the Mini-Symposium on Cancer Pharmacoepidemiology.

Ann Epidemiol. 2016 11;26(11):749-750

Authors: Walker AM

PMID: 27637749 [PubMed - indexed for MEDLINE]

Resminostat in patients with relapsed or refractory Hodgkin lymphoma: results of the phase II SAPHIRE study.

Leuk Lymphoma. 2018 Aug 30;:1-10

Authors: Walewski J, Paszkiewicz-Kozik E, Borsaru G, Hellmann A, Janikova A, Warszewska A, Mais A, Ammendola A, Herz T, Krauss B, Henning SW

Abstract
This open-label, single-arm phase II study examined efficacy, safety, pharmacokinetics, and biomarkers of histone deacetylase (HDAC) inhibitor resminostat in patients with relapsed or refractory Hodgkin lymphoma. Thirty-seven heavily pretreated patients received 600 (19 patients) or 800 mg (18 patients) oral resminostat daily for the initial 5 days of 14-day treatment cycles. Objective response rate (ORR) (primary) was 34% reaching disease control in 54% patients. Most patients (69%) showed reduced tumor size and reduced [18F]-FDG uptake in target lesions (71%). Median progression-free survival (PFS) was 2.3 months (95%CI [1.3; 3.3]) and median overall survival (OS) was 12.5 months (95%CI [9.6; 18.6]). Patients who responded or stabilized under resminostat had a 10-month longer OS than patients who progressed. Efficacy assessment, pharmacodynamics, and exploratory biomarker results followed plasma levels, showed target engagement and epigenetic modulations. Common drug-related adverse events (AEs) were nausea, vomiting, anemia, thrombocytopenia, and fatigue, mainly grade 1 or 2.

PMID: 30160566 [PubMed - as supplied by publisher]

Minimal Use of Opioids for Pain Relief in an Internal Medicine Department.

South Med J. 2018 05;111(5):288-292

Authors: Shimoni Z, Varon D, Froom P

Abstract
OBJECTIVES: The objective of the study was to determine if pain control was adequate despite our policy of limited opioid use.
METHODS: In this observational cohort study, we reviewed 300 consecutive patient charts from an internal medicine department. We extracted demographic data, as well as the patients' primary diagnosis, pain on admission, daily pain evaluations (numerical rating score [NRS]), and treatment. Significant pain was defined as a score of ≥3 on the NRS. We determined the incidence of pain and pain control and reviewed the charts of those with an NRS ≥3 for ≥3 days to determine the need for opioid therapy.
RESULTS: Of 1692 total hospitalization days in the 300 consecutive patients with a median age of 80 years (1st-3rd quartiles, 65-87 years) there were 204 days with complaints of pain (12.1%) and 149 days (8.8%) with reports of pain of ≥3 on the NRS. Overall, 28.3% (85 of 300) of the patients had significant pain during their hospitalization. Most of the pain, however, (80.0%, 68 of 85) was short-term (1-2 days) whether or not the patient received pain medication. Pain relief treatment in the hospital included opioids in 17 (5.7%, 95% confidence interval [CI] 3.5-8.9) and dipyrone in 36 (12%, 95% CI 8.8-16) of the 300 patients. Pain control was adequate in the seven patients with prolonged pain who did not receive opioids. There were only two patients discharged with prescriptions for opioids (0.7%, 95% CI 0.2-2.6).
CONCLUSIONS: Significant pain is common in patients hospitalized in an internal medicine department, but the pain is mostly short term and pain control is adequate despite the restricted use of opioid therapy during hospitalization.

PMID: 29767221 [PubMed - indexed for MEDLINE]

Effectiveness and the strategy to treat the side effects of sorafenib administration after transarterial chemoembolization in advanced hepatocellular carcinoma patients.

J Cancer Res Ther. 2018 Jan;14(1):196-200

Authors: Zhang K, Sun X, Xie F, Jian W, Li C

Abstract
Objective: The aim is to study the effectiveness and side effects of sorafenib administration after transarterial chemoembolization (TACE) in advanced hepatocellular carcinoma (HCC) patients. To evaluate the safety of the combination of sorafenib and TACE to treat HCC.
Materials and Methods: A total of 36 unresectable HCC patients were enrolled. After TACE, administration of sorafenib was carried out. Follow-up was taken for every 4 weeks. Liver and renal function and alpha-fetoprotein were tested. Modified response evaluation criteria in solid tumors (mRECIST) was used to evaluate the clinical effect. The side effects were recorded.
Results: The median overall survival (mOS) and the median time to progress were 12.5 and 8 months with the range from 6 to 32 and 4-30 months, respectively. The mOS of patients with single tumor was 18 months while that of multiple tumors in liver was 10 months (χ2 = 4.1639, P = 0.0413). According to mRECIST, there were no complete response patients, 2 partial response patients, 10 stable disease patients, and 24 progressive disease patients. Response rate was 5.5% (2/36). Disease control rate (DCR) was 33% (12/36). The main adverse events were hand-foot skin reaction and diarrhea. The frequency of Grade II, III hand-foot-skin reaction was 39%. After treatment, it decreased to 5.6%. Forty-four percentage patients suffered from diarrhea of Grades I and II. After treatment, it decreased to 28%. The mean interval of TACE was 45 days before combination therapy and 120 days after combination therapy.
Conclusion: Administration of sorafenib after TACE could prolong overall survival of advanced HCC patients, keep the stable status longer and extend the interval between TACEs. The side effects are usually treatable, which proves the safety of this combination.

PMID: 29516985 [PubMed - indexed for MEDLINE]

Anticoccidial activity of fruit peel of Punica granatum L.

Microb Pathog. 2018 Mar;116:78-83

Authors: Ahad S, Tanveer S, Malik TA, Nawchoo IA

Abstract
In the interests of food safety and public health, plants and their compounds are now re-emerging as an alternative approach to treat parasitic diseases. Here, we studied the anticoccidial effect of different solvent extracts of the fruit peel of Punica granatum-a commercial waste from pomegranate juice industries. The hope underlying these experiments was to find a sustainable natural product for controlling coccidiosis. The plant extracts were prepared using solvents of different polarity. Acute oral toxicity study was first carried out to see the safety of crude extracts. A high dose of crude extracts (300 mg/kg body weight) was tested for possession of anticoccidial activity against experimentally induced coccidial infection in broiler chicken. Activity was measured in comparison to the reference drug amprolium on the basis of oocyst output reduction, mean weight gain of birds and feed conversion ratio. Oocyst output was measured using Mc-Masters counting technique. Acute oral toxicity study showed that crude extracts of P. granatum are safe up to dosage of 2000 mg/kg body weight. LD50 was not determined as mortalities were not recorded in any of the five groups of chicken. For anticoccidial activity crude methanolic extract (CME) of the fruit peel of P. granatum showed the maximum effect as evident by oocyst output reduction (92.8 ± 15.3), weight gain of birds (1403.0 ± 11.9 g) and feed conversion ratio (1.66 ± 0.04), thereby affirming the presence of alcohol soluble active ingredients in the plant. We also tested different doses (100-400 mg/kg body weight) of the CME of the fruit peel of P. granatum, the most active extract on E. tenella and observed a dose dependent effect. From the present study it can be concluded that alcoholic extract of the fruit peel of P. granatum has significant potential to contribute to the control of coccidian parasites of chicken.

PMID: 29339307 [PubMed - indexed for MEDLINE]

Improving drug allergy management in Australia: education, communication and accurate information.

Med J Aust. 2018 Sep 03;

Authors: Lucas M, Loh RK, Smith WB

PMID: 30157407 [PubMed - as supplied by publisher]

Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Endothelial Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer.

J Clin Oncol. 2018 Aug 29;:JCO2018777326

Authors: Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, Chia V, Glaser S, Pultar P, Zhao S, Peng B, Akimov M, Tan DSW

Abstract
Purpose Mesenchymal-epithelial transition factor (MET) dysregulation occurs in up to 26% of non-small-cell lung cancers (NSCLCs) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Capmatinib (INC280) is a potent and selective MET inhibitor with preclinical activity in combination with gefitinib in EGFR-mutant, MET-amplified/overexpressing models of acquired EGFR-TKI resistance. This phase Ib/II study investigated the safety and efficacy of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated (amplified/overexpressing) NSCLC who experienced disease progression while receiving EGFR-TKI treatment. Methods Patients in phase Ib received capmatinib 100- to 800-mg capsules once per day or 200- to 600-mg capsules or tablets twice per day, plus gefitinib 250 mg once per day. Patients in phase II received the recommended phase II dose. The primary end point was the overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results Sixty-one patients were treated in phase Ib, and 100 were treated in phase II. The recommended phase II dose was capmatinib 400 mg twice per day plus gefitinib 250 mg once per day. Preliminary clinical activity was observed, with an ORR across phase Ib/II of 27%. Increased activity was seen in patients with high MET-amplified tumors, with a phase II ORR of 47% in patients with a MET gene copy number ≥ 6. Across phases Ib and II, the most common drug-related adverse events were nausea (28%), peripheral edema (22%), decreased appetite (21%), and rash (20%); the most common drug-related grade 3/4 adverse events were increased amylase and lipase levels (both 6%). No significant drug-drug interactions between capmatinib and gefitinib were evident. Conclusion This study, focused on a predominant EGFR-TKI resistance mechanism in patients with EGFR-mutated NSCLC, shows that the combination of capmatinib with gefitinib is a promising treatment for patients with EGFR-mutated, MET-dysregulated NSCLC, particularly MET-amplified disease.

PMID: 30156984 [PubMed - as supplied by publisher]