Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase which becomes oncogenic and drives tumor growth in multiple tumor types, including non-small cell lung cancer (NSCLC). We discuss the pathophysiology of ALK in NSCLC, which is driven predominantly by ALK gene rearrangements. We review the various methods of molecular testing for ALK gene rearrangements in NSCLC, and their limitations.
Oral Tyrosine Kinase Inhibitors (TKIs) targeting the ALK pathway have been rapidly developed in the past 10 years. These drugs are well tolerated and offer prolonged disease control. We highlight the most up-to-date clinical data for each of the agents currently available which target the ALK pathway, and discuss adverse events associated with each agent. We discuss mechanisms of resistance to the ALK-targeted TKIs, and options for treatment at disease progression. READ ARTICLE

Encyclopedia of Respiratory Medicine (Second Edition) DOI:10.1016/B978-0-12-801238-3.11701-5

Authors: Maria Coakley, Sanjay Popat

EML4-ALK G1202R mutation induces EMT and confers resistance to ceritinib in NSCLC cells via activation of STAT3/Slug signaling

The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene occurs in approximately 5% of non-small-cell lung cancers (NSCLCs). The development of ALK tyrosine kinase inhibitors (ALK-TKIs) is a major advance in treating NSCLC with the ALK fusion gene. Nevertheless, acquired resistance to ALK-TKIs ultimately limits their use. A prevalent mechanism of drug resistance in kinases occurs through the mutation of G1202R in ALK. However, the mechanisms underlying G1202R resistance to ceritinib are not fully understood. Here, we demonstrated that the expression of EML4-ALK G1202R mutation in A549 cells induced an epithelial-mesenchymal transition (EMT) phenotype and significantly increased the migration and invasion abilities. These phenomena may be due to the upregulation of signal transducer and activator of transcription 3 (STAT3), accompanied by the elevated expression of Slug in EML4-ALK G1202R mutant cells. Furthermore, the combination of ALK and STAT3 inhibitors restored the sensitivity of EML4-ALK G1202R mutant cells to ceritinib. In conclusion, these data indicate that the EML4-ALK G1202R mutation mediates the EMT phenotype by activating the STAT3/Slug signaling pathway, resulting in resistance to ceritinib, and that the combination of STAT3 and ALK inhibitors may overcome ALK mutation-driven drug resistance in the clinic. READ ARTICLE

Cellular Signalling DOI:10.1016/j.cellsig.2022.110264

Authors: Jiwei Shen, Yuting Meng, Kunlun Wang, Minghuan Gao, Jianan Du, Junfang Wang, Zengqiang Li, Daiying Zuo, Yingliang Wu

Case StudyKirk SmithApril 1, 2022EML4-ALK G1202R mutation, EMT, STAT3, Slug, Resistance, Ceritinib

Genetic landscape of patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study

NGS data were generated for 85 pts (ALKi-pretreated [n = 54]; ALKi-naïve [n = 31]), 57 were collected from patients before exposure to any ALKi. NGS did not detect ALK rearrangement in 14 of 85 patients; several of these ALK NGS negative cases harbored alternative drivers, e.g. EGFR mutation. Of the 71 biopsies with NGS confirmed ALK rearrangement, the most frequently detected rearrangements were EML4-ALK variant 1 (V1) and EML4-ALK V3 (36.6% [26/71] and 32.4% [23/71] respectively). Eight (six crizotinib-pretreated and two pretreated with crizotinib followed by alectinib) of the 21 ALKi-pretreated patients carried a point mutation of the ALK TKD, and had the biopsy collected between 1 and 14 days before ceritinib; with the exception of one patient with a G1202R point mutation, all patients derived clinical benefit from ceritinib treatment.
Of the 14 ALKi-naïve patients, ceritinib was effective in almost all patients, including a patient carrying a concomitant ERBB4 and HGF amplificatio..... READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.11.007

Authors: D.S-W.Tana, M.Thomas, DW.Kim, S. Szpakowski, P. Urban, R. Mehra, L.Q.M. Chow, S. Sharma, B.J. Solomon, E.Felip, D.R. Camidge, J. Vansteenkiste, L. Petruzzelli, S. Pantano and A.T. Shaw

Genetic landscape of patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and response to ceritinib in ASCEND-1 study

Objectives: To better understand genetic determinants of response to ceritinib, an exploratory analysis was conducted using tumor biopsies from anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients treated with ceritinib at doses of ≥ 300 mg in the ASCEND-1 study. Conclusions: This exploratory analysis highlights the potential role of NGS in improving our understanding of response and resistance to ceritinib. It also illustrates that ceritinib is active against almost all ALK resistance mutations found in ALKi-pretreated patients. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.11.007

Authors: D S-W Tan, M Thomas, D-W Kim, S Szpakowski, P Urban, R Mehra, L Q M Chow, S Sharma, B J Solomon, E Felip, D R Camidge, J Vansteenkiste, L Petruzzelli, S Pantano, A T Shaw

Assessment of Alectinib vs Ceritinib in ALK-Positive Non–Small Cell Lung Cancer in Phase 2 Trials and in Real-world Data

How robust are conclusions about the comparative effectiveness of the ALK inhibitor alectinib vs ceritinib in crizotinib-refractory, ALK-positive non–small cell lung cancer from indirect comparisons using real-world data (RWD)? This comparative effectiveness study including 355 patients found that alectinib exposure was associated with improved survival compared with ceritinib in both single-group trials and multicenter US RWD. Results were robust to a range of plausible assumptions about unmeasured confounding and missing Eastern Cooperative Oncology Group Performance Status and underrecorded comorbidities in RWD. Alectinib exposure was associated with longer OS compared with ceritinib in patients with ALK-positive NSCLC, and only substantial levels of bias examined reversed the findings. These findings suggest that quantitative bias analysis can be a useful tool to address uncertainty of findings for decision-makers considering RWD. READ ARTICLE

JAMA Network Open DOI:10.1001/jamanetworkopen.2021.26306

Authors: Wilkinson S, Gupta A, Scheuer N, Mackay E, Arora P, Thorlund K, Wasiak R, Ray J, Ramagopalan S, Subbiah V.

Clinical Trials, group2Kirk SmithOctober 1, 2021Alectinib, Ceritinib, Non–Small Cell Lung Cancer, Trials

Development and validation of UPLC–MS/MS method for the simultaneous quantification of anaplastic lymphoma kinase inhibitors, alectinib, ceritinib, and crizotinib in Wistar rat plasma...

Bromelain, the aqueous extract of pineapple, has been used as a food supplement with reported nutritional and therapeutic benefits. Bromelain has anti-cancer, anti-inflammatory, antithrombotic, and fibrinolytic effects. Anaplastic lymphoma kinase (ALK) inhibitors, including alectinib (ALC), ceritinib (CER), and crizotinib (CRZ), have been efficiently used in the management of non-small cell lung cancer (NSCLC). The solubility of ALC, CER, and CRZ is much higher at low acidic pH (pH 1) and it decreases as the pH increases affecting their absorption with a subsequent decrease in their bioavailability. It was thought that the intake of bromelain could result in a decrease in the bioavailability of ALC, CER, and CRZ due to bromelain-induced alkalizing effect following digestion. On the contrary, bromelain could possibly increase plasma exposure of the cited drugs due to its known muco-permeation enhancing effect. The therapeutic-anticancer effect of bromelain can be possibly increased/enha..... READ ARTICLE

Journal of Pharmaceutical and Biomedical Analysis DOI:10.1016/j.jpba.2021.114276

Authors: Hadir M. Maher, Aliyah Almomen, Nourah Z. Alzoman, Shereen M. Shehata, Ashwaq A. Alanazi

ALK Inhibitors Do Not Increase Sensitivity to Radiation in EML4-ALK Non-small Cell Lung Cancer

ALK inhibitors like Crizotinib, Ceritinib and Alectinib are targeted therapies used in patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC). Since in this tumor entity radiotherapy is employed sequentially or concomitantly, potential synergistic effects were investigated, which may support the hypothesis of induced radiosensitization by using ALK inhibitors. Two cell lines expressing wild-type (WT) or echinoderm microtubule-associated protein-like 4 (EML4)-ALK were treated with ALK inhibitors, followed by irradiation. Cell survival, cell death, cell cycle and phosphorylation of H2A histone family, member X (H2AX) were examined. Combined treatment with ALK-inhibitors plus 10 Gy-irradiation led to effects similar to those of sole radiotherapy, but was more effective than sole drug treatment. There is no clear evidence of sensitization to radiation by treating EML4-ALK mutated cells with ALK inhibitors. READ ARTICLE

Anticancer Research DOI:10.21873/anticanres.14497

Authors: Kathrin Fleschutz, Lisa Walter, Tumo Leistner, Lucie Heinzerling

Forced degradation of Ceritinib under stress conditions: Structural interpretation of novel degradants using HR-MS/MS and NMR

The current work describes the preparative isolation and structural interpretation of acid degradation product of ceritinib (CRB). The drug is exposed to different stress conditions (acid, base hydrolysis, oxidation, thermal and photolytic) as suggested by International Conference on Harmonisation guidelines (ICH). The degradation of drug (CRB) is observed when exposed to acidic condition whereas the drug is stable in remaining stress conditions. The separation between drug and acid degradant was attained on a C18 BEH UPLC column (50 mm × 2.1 mm, 1.7 μm) in a gradient separation mode. The mobile phase comprises of acetonitrile and 0.05% formic acid buffer at a flow rate of 0.6 mL/min and UV wavelength monitored at 215 nm. One novel degradation product formed in acidic condition was isolated by Preparative HPLC (Prep-HPLC). Structural interpretation and characterisation done by HR-MS/MS and NMR studies which is not yet described in the literature. READ ARTICLE

Materials Today: Proceedings DOI:10.1016/j.matpr.2020.01.588.

Authors: Soujanya Vajjha, Vijay Bommuluri, Chidananda Swamy Rumalla, Muralidharan Kaliyaperumal, Raghu Babu Korupolu, Vidyasagar chopella

Pre-ClinicalKirk SmithJuly 12, 2020Ceritinib, Drug degradation, Structural elucidation

Recurrent hyperglycemic hyperosmolar state after re-administration of dose-reduced ceritinib, an anaplastic lymphoma kinase inhibitor

Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor with clinical activity in crizotinib-resistant ALK-positive non-small cell lung cancer and in treatment-naïve ALK-positive disease. Hyperglycemia is a known adverse event, but the mechanism by which ceritinib causes hyperglycemia is unknown, and whether ceritinib causes hyperglycemic emergencies is unclear. Here, we report the case of a patient with a hyperglycemic hyperosmolar state (HHS) recurrence after the re-administration of dose-reduced ceritinib. A 78-year-old man with type 2 diabetes diagnosed as having advanced lung adenocarcinoma had been treated with alogliptin (25 mg/day) for the diabetes and with ceritinib for the lung cancer. After 28 days of ceritinib administration, he was admitted to our hospital due to HHS. His blood glucose level improved with insulin therapy after discontinuation of the ceritinib. He then received re-administration with a decreased ceritinib dose while maintaining the insul..... READ ARTICLE

Diabetology International DOI:10.1007/s13340-020-00442-w

Authors: Miyoshi, Y., Ogawa, O., Nishida, A. et al.

Real world experience of treatment and outcome in ALK-rearranged metastatic nonsmall cell lung cancer: A multicenter study from India

Background: Anaplastic lymphoma kinase (ALK) rearranged metastatic non-small cell lung cancer (NSCLC) comprises 5%-7% of all lung cancer and carries a good prognosis with available ALK-inhibitors. Majority of registration trials in ALK-inhibitors did not include Indian patients. Hence, this study was planned to analyze the outcome of Indian patients treated with ALK-inhibitors and associated challenges. Results: A total of 274 patients were studied, out of which 250 patients received ALK inhibitor and were analyzed further for outcome. The median age was 50 years (range: 24-82) and male to female ratio of 1.17:1. ALK was evaluated by immunohistochemistry in majority of patients (97%), 3 patients by FISH and 3 more patients were evaluated by both methods. Sixty-five percent (n = 162) of the patients received ALK-inhibitor as first line therapy, 51 patients received ALK-inhibitor as switch maintenance therapy after initial chemotherapy. Crizotinib and Ceritinib were used in 88% and 12%,..... READ ARTICLE

Cancer DOI:10.1016/j.currproblcancer.2020.100571.

Authors: Amol Patel, Ullas Batra, Kuruswamy Thurai Prasad, Deepak Dabkara, Joydeep Ghosh, Manasi Sharma, Navneet Singh, P. Suresh, Parveen Jain, Prabhat Singh Malik, Priyanshu Choudhary, Sandip Ganguly, Sachin Khurana, Shivashankara MS, Sneha Bothra, Valliappan Muthu, Bivas Biswas,

Anaplastic Lymphoma Kinase Mutation–Positive Non–Small Cell Lung Cancer

KEY POINTS:
Non–small cell lung cancer with anaplastic lymphoma kinase (ALK) chromosomal rearrangement is
sensitive to treatment with tyrosine kinase inhibitors (TKIs).
Numerous TKIs have been developed in recent years, including alectinib, which is the current
preferred first-line agent for treatment-naı¨ve patients.
The development of resistance has led to next-generation ALK inhibitors that better penetrate the
central nervous system, which has improved the treatment of brain metastasis. READ ARTICLE

Thoracic Surgery Clinics DOI:10.1016/j.thorsurg.2019.12.001

Authors: Anthony V. Serritella, Christine M. Bestvina

Transformation of EML4-ALK fusion-positive adenocarcinoma into squamous cell carcinoma in association with acquired resistance to crizotinib

Background: Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. Conclusions: This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression. READ ARTICLE

BMC Cancer DOI:10.1186/s12885-019-6486-3

Authors: F. Guisier, N. Piton, M. Bellefleur, N. Delberghe, G. Avenel, E. Angot, O. Vittecoq, M. Ould-Slimane, H. Morisse-Pradier, M. Salaun, L. Thiberville

Case StudyKirk SmithJanuary 6, 2020ALK-rearranged NSCLC, ALK inhibitors, Crizotinib, Ceritinib, Drug toxicity, Osteitis

Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3: Phase II Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC

Introduction: The phase II, single-arm ASCEND-3 study assessed the efficacy and safety of ceritinib in anaplastic lymphoma kinase (ALK) inhibitor (ALKi)–naive patients with ALK-rearranged NSCLC who had received at least three previous lines of chemotherapy. Here, we report the final efficacy and safety results. Conclusions: Ceritinib exhibited prolonged and clinically meaningful OS, PFS, and duration of response in chemotherapy-pretreated (at least three lines), ALKi-naive patients with ALK+ NSCLC. The safety profile was consistent with that reported in previous studies. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.11.006

Authors: Makoto Nishio, Enriqueta Felip, Sergey Orlov, Keunchil Park, Chong-Jen Yu, Chun-Ming Tsai, Manuel Cobo, Mark McKeage, Wu-Chou Su, Tony Mok, Giorgio V. Scagliotti, David R. Spigel, Kalyanee Viraswami-Appanna, Zhe Chen, Vanessa Q. Passos, Alice T. Shaw

Clinical TrialsKirk SmithNovember 25, 2019Ceritinib, ALK, NSCLC, Phase II, ASCEND-3

Ceritinib plus Nivolumab in Patients with Advanced ALK-Rearranged Non–Small Cell Lung Cancer: Results of an Open-Label, Multicenter, Phase 1B Study

Induction of programmed death ligand 1 (PD-L1) expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring echinoderm microtubule associated protein like 4 gene (EML4)–ALK receptor tyrosine kinase gene (ALK) rearrangements. We assessed the safety and activity of ceritinib plus nivolumab in these patients.In this open-label, phase 1B, multicenter, dose escalation and expansion study, previously treated (with ALK receptor tyrosine kinase [ALK] inhibitor [ALKI]/chemotherapy) or treatment-naive patients with stage IIIB or IV ALK-rearranged NSCLC received nivolumab, 3 mg/kg intravenously every 2 weeks, plus ceritinib, 450 mg/300 mg daily, with a low-fat meal. Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.10.006

Authors: Enriqueta Felip, Filippo G. de Braud, Michela Maur, Herbert H. Loong, Alice Tsang Shaw, Johan F. Vansteenkiste, Thomas John, PGeoffrey Liu, Martijn P. Lolkema, Giovanni Selvaggi, Vanessa Giannone, Pilar Cazorla, Jason Baum, O. Alejandro Balbin, Luojun (Victor) Wang, Yvonne Y. Lau, Jeffrey W. Scott, Daniel Shao-Weng Tan

Clinical TrialsKirk SmithOctober 18, 2019Ceritinib, Nivolumab, ALK, PD-1, NSCLC

EP114-02 Comparative Efficacy of First-Line Ceritinib at a Dose of 450mg with Food and Alectinib in Advanced ALK+ NSCLC

Ceritinib and alectinib were both second generation of ALK inhibitors that approved as first-treatment for ALK+ NSCLC. Ceritinib is initially approved at the recommended dose of 750 mg/day fasted (ceritinib 750-mg fasted). Ceritinib at a dose of 450 mg with food (ceritinib 450-mg fed) compared to ceritinib 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity in the Ascend 8 trial. Although a previous cross-study indirect study compared the efficacy of ceritinib 750-mg fasted with alectinib, the efficacy of ceritinib 450-mg fed compared with alectinib is unknown. Progression-free survival of ceritinib 450-mg fed was indirectly compared with that of alectinib using a Bucher anchor-based indirect comparison approach using ceritinib 750-mg fasted as the common anchor. The comparative efficacy of alectinib vs ceritinib 750-mg fasted was obtained from matching-adjusted indirect comparison(MAIC) and the comparative efficacy of ceritinib 450-mg fed vs ceritinib 750-mg fa..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2287

Authors: F. Liang, D. Shen

Conference PaperKirk SmithOctober 1, 2019ALK, Ceritinib, alectinib]

P116-46 Genetic Testing Patterns, Treatment Characteristics, and Overall Survival in ALK-Positive Metastatic NSCLC Patients Treated with Ceritinib

This study therefore sought to assess ALK testing patterns, treatment characteristics, and overall survival (OS) in patients with mNSCLC treated with ceritinib in routine practice.87 patients were selected (median age: 53 years). Nearly 56% of patients had been tested for ALK mutation before initiating the first-line therapy (1L); 72% were tested before 2L and 77% before 3L. The most common regimens were cisplatin/pemetrexed (25%) in 1L, crizotinib (28%) in 2L, and ceritinib (35%) in 3L. Over two-thirds (68%) received treatment with at least 2 ALKis. The most commonly observed ALKi sequences were crizotinib followed by ceritinib (52%), ceritinib only (23%), and crizotinib followed by ceritinib followed by alectinib (12%). Median OS (95% CI) from mNSCLC diagnosis was 39 (33.1-50.1) months. Median OS (95% CI) from treatment initiation was 36 (28.2-48.9) months for 1L, 29 (22.1-42.8) months for 2L, and 23 (14.0-40.5) months for 3L. Only slightly more than half of patients with ALK-positi..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1272

Authors: J. Mazieres, M. Ahn, C. Chouaid, A. Kron, J. Wolf, R. Goyal, K. Davis, M. Perrinjaquet, T. Pham, S. Knoll

Conference PaperKirk SmithOctober 1, 2019ALK, metastatic NSCLC, Ceritinib

EP101-62 The Safety Profile and Preliminary Efficacy of Ceritinib 450mg with Food in Chinese ALK/ROS-1 Positive NSCLC Patients

Ceritinib have shown potent efficacy in both ALK and ROS-1 rearranged NSCLC. However, high rate of treatment interruption was suffered due to gastrointestinal or liver toxicity using Ceritinib 750mg fasting in previous study. Recently, ASCEND-8 study reported an improved tolerance and a trend to better efficacy with 450mg with food, but little data is available in Chinese patients. This first-time real-world study aims to assess the safety profile and preliminary efficacy of Ceritinib 450mg with food in Chinese patients. From Oct 2018 to March 2019, 51 ALK or ROS1 positive NSCLC patients received ceritinib were enrolled from 8 centers in Sichuan province. Safety profile and preliminary efficacy were retrospectively analyzed. The follow-up was to 31st March 2019. The study found Ceritinib 450mg with food demonstrated a good safety profile and efficacy with lower AE incidence rate and better compliance rate compare to ASCEND-8 data for Chinese patients in real-world setting...... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.2035

Authors: Y. Tian, P. Yu, X. Yin, K. Wang, M. Huang, Y. Wang, Y. Gong, J. Li

Conference PaperKirk SmithOctober 1, 2019Ceritinib, non-small-cell lung cancer, Safety

Design, synthesis of orally bioavailable novel anaplastic lymphoma kinase (ALK) inhibitor diphenylaminopyrimidine analogs and efficacy study on NCI-H2228 xenografts mice model

Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of non-small cell lung cancer (NSCLC). Within our ALK drug discovery program, we identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound 11 showed better in vitro activity and in vivo efficacy with good pharmacokinetic profile. In vivo efficacy of compound 11 was better than standard drug ceritinib in NCI-H2228 xenograft mice model. READ ARTICLE

Bioorganic & Medicinal Chemistry Letters DOI:10.1016/j.bmcl.2019.04.012

Authors: Debasis Das, Jingbing Wang, Yong Li, Jingli Shi, Jian Hong

Application of time-dependent modeling for the exposure-efficacy analysis of ceritinib in untreated ALK-rearranged advanced NSCLC patients

Purpose: Ceritinib 750 mg/day was approved for the treatment of patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) based on ASCEND-4 study. The objective of this article is to introduce the use of time-dependent modeling approach in the updated exposure-efficacy analysis of ceritinib for the first-line indication. READ ARTICLE

Cancer Chemotherapy and Pharmacology DOI:10.1007/s00280-019-03830-5

Authors: Yvonne Y Lau, Wen Gu, Yu-Yun Ho, Ying Hong, Xinrui Zhang and Patrick Urban

Efficacy and Safety of Ceritinib (450 mg/d or 600 mg/d) With Food Versus 750-mg/d Fasted in Patients With ALK Receptor Tyrosine Kinase (ALK)–Positive NSCLC

Introduction: In an earlier report of the ASCEND-8 study (open-label, phase I, three-arm study, treatment-naive patients and pre-treated patients with advanced/metastatic NSCLC), it was shown that ceritinib 450 mg with food had comparable exposure and better gastrointestinal tolerability than 750-mg fasted. Conclusion: Ceritinib at a dose of 450 mg with food compared to 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.03.002

Authors: Byoung Chul Cho, Radka Obermannova, Alessandra Bearz, Mark McKeage, Dong-Wang Kim, Ullas Batra, Gloria Borra, Sergey Orlov, Sang-We Kim, Sarayut L. Geater, Pieter E. Postmus, Scott A. Laurie, Keunchil Park, Cheng-Ta Yang, Andrea Ardizzoni, Anna C. Bettini, Gilberto de Castro Jr., Flavia Kiertsman, Zhe Chen, Yvonne Y. Lau, Kalyanee Viraswami-Appanna, Vanessa Q. Passos, Rafal Dziadziuszko