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

Alectinib Monotherapy in Isolated Central Nervous System Relapse of ALK-Positive Anaplastic Large Cell Lymphoma

Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-positive ALCL) is an aggressive form of peripheral T cell lymphoma (PTCL), harbouring an underlying pathogenic ALK fusion gene that produces a constitutively activated tyrosine kinase. The ALK tyrosine kinase provides a targeted treatment option in the form of ALK inhibitors. ALK-positive ALCL may rarely involve the central nervous system (CNS), either at presentation or on relapse of disease. The outcomes of CNS relapse in PTCL are historically extremely poor. We present a case of a 20-year-old man diagnosed with stage IVB ALK-positive ALCL. He responded favourably to six cycles of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP). He unfortunately relapsed with isolated CNS involvement only 3 weeks after completing his sixth cycle of CHOEP chemotherapy. The CNS-penetrating ALK inhibitor alectinib was identified as a targeted treatment option, as he was not a candidate for CNS-penetrating chemotherapy due to significant iatrogenic renal impairment. After commencing alectinib monotherapy, he rapidly achieved a clinical and radiological response. He has now remained in a durable remission for more than two years on alectinib monotherapy. READ ARTICLE

Case Reports in Hematology DOI:10.1155/2022/4749452

Authors: Julian Verran, Vidya Mathavan

Case StudyKirk SmithFebruary 3, 2022Alectinib, Central Nervous System, Anaplastic Large Cell Lymphoma

Influence of alectinib and crizotinib on ionizing radiation - in vitro analysis of ALK/ROS1-wildtype lung tissue cells

(1) Background: Just little is known about the interaction of ALK/ROS1-targeting kinase inhibitors with ionizing radiation (IR), particularly regarding side effects. We investigated the toxicity in two different lung cell lines both ALK/ROS1 wildtype (healthy and tumor origin) as representatives for normal lung tissue; (2) Methods: Human lung cell line BEAS-2B and malignant A549 lung cancer cells (ALK/ROS1 wt) were treated with alectinib or crizotinib, 2 Gy irradiation or a combination of KI and IR. Cell toxicity was analyzed by cell death (Annexin, 7AAD), colony forming, migration assay and live-cell imaging (TMRM, DRAQ7, Caspase3/7). Cell cycle (Hoechst) were analyzed by flow cytometry; (3) Results: Crizotinib led to higher cell death rates than alectinib, when cells were treated with 10 µM KI. Alectinib induced a more intense growth inhibition of colonies. Both inhibitors showed additive effects in combination with irradiation. Combination treatment (IR + KI) does not lead to synergistic effect on neither cell death nor colony forming; (4) Conclusions: The influence of simultaneous KI and IR was studied in non-mutated ALK/ROS1 cell lines. Both KIs seems to be well tolerated in combination with thoracic radiotherapy and lacked synergistic reinforcement in cellular toxicity. This supports the feasibility of ALK/ROS1 inhibition in combination with thoracic irradiation in future clinical trials. READ ARTICLE

Neoplasia DOI:10.1016/j.neo.2022.100780

Authors: Tina Jost, Ann-Kristin Schultz, Benjamin Frey, Jennifer Vu, Rainer Fietkau, Luitpold V. Distel, Markus Hecht

Review PaperKirk SmithFebruary 1, 2022Lung cells, Alectinib, Crizotinib, Radiotherapy, Normal tissue, Side effects

Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases—a multicenter retrospective study

Central nervous system (CNS) metastases in patients with ALK-positive non-small cell lung cancer (NSCLC) are a cause of substantial morbidity and mortality. Although alectinib had demonstrated promising intracranial efficacy in several clinical trials, data were limited on its CNS activity in real-world settings. Our study substantiated the potent CNS activity of alectinib in real-world settings. Patients with symptomatic and asymptomatic BM could benefit from alectinib comparatively, which indicated that alectinib alone might defer the timing of local treatment. However, our results should be treated cautiously owing to limited sample size. READ ARTICLE

BMC Med DOI:10.1186/s12916-021-02207-x

Authors: Zou Z, Xing P, Hao X, Wang Y, Song X, Shan L, Zhang C, Liu Z, Ma K, Dong G, Li J.

Case Report: A Novel Non-Reciprocal ALK Fusion: ALK-GCA and EML4-ALK Were Identified in Lung Adenocarcinoma, Which May Respond to Alectinib Adjuvant-Targeted Therapy

Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancers (NSCLCs) have favorable and impressive response to ALK tyrosine kinase inhibitors (TKIs). However, ALK rearrangement had approximately 90 distinct fusion partners. Patients with different ALK fusions might have distinct responses to different-generation ALK-TKIs. In this case report, we identified a novel non-reciprocal ALK fusion: ALK-grancalcin (GCA) (A19: intragenic) and EML4-ALK (E20: A20) by next-generation sequencing (NGS) in a male lung adenocarcinoma patient who was staged as IIIB-N2 after surgery. After a multidisciplinary discussion, the patient received alectinib adjuvant targeted therapy and postoperative radiotherapy (PORT). He is currently in good condition, and disease-free survival (DFS) has been 20 months so far, which has been longer than the median survival time of IIIB NSCLC patients. Our study extended the spectrum of ALK fusion partners in ALK + NSCLC, and we reported a new ALK fusion: ALK-GCA a..... READ ARTICLE

Frontiers in Oncology DOI:10.3389/fonc.2021.782682

Authors: Zhai Xiaoqian, Wu Qiang, Pu Dan, Yin Liyuan, Wang Weiya, Zhu Daxing, Xu Feng

Case StudyKirk SmithJanuary 5, 2022ALK-GCA, EML4-ALK, Alectinib, non-reciprocal ALK rearrangement

Is Elevation of Alkaline Phosphatase a Predictive Factor of Response to Alectinib in NSCLC?

In the following report, we describe a case of alkaline phosphatase (ALP) elevation occurring during treatment with alectinib (Alecensa™), which was administered for anaplastic lymphoma kinase (ALK) mutated metastatic non-small cell lung cancer (mNSCLC). A 51 year-old female with widespread metastatic disease exhibited a rapid and significant response within a very short period to alectinib therapy, accompanied by a rapid increase of ALP to more than six times the upper limit of normal (grade 3) ALP, decreasing to within normal limits within 3 weeks after initiation of therapy without any dose modification. READ ARTICLE

Current Oncology DOI:10.3390/curroncol29010016

Authors: Walid Shalata, Alexander Yakobson, Rachel Steckbeck, Ashraf Abu Jama, Omar Abu Saleh and Abed Agbarya

Case Study, group1Kirk SmithDecember 31, 2021lung adenocarcinoma, ALK mutation, Alectinib, alkaline phosphatase, toxicity

Clinical outcome, long-term survival and tolerability of sequential therapy of first-line crizotinib followed by alectinib in advanced ALK+NSCLC: A multicenter retrospective analysis in China

There is limited data on the clinical outcome, long-term survival and tolerability of sequential therapy of first-line crizotinib followed by alectinib in a real-world setting for Chinese patients with advanced ALK+ NSCLC. The medical records of patients who received sequential therapy with first-line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK-TKIs) were collected from six centers in China. Combined time treatment to failure (C-TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause.
A total of 61 patients were included in our study. Fifty-two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patien..... READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.14232

Authors: Zihua Zou, Xuezhi Hao, Cuiying Zhang, Haojing Li, Guilan Dong, Yumei Peng, Kewei Ma, Ye Guo, Li Shan, Yan Zhang, Li Liang, Yangchun Gu, Puyuan Xing, Junling Li

Real-World OutcomesKirk SmithDecember 1, 2021Alectinib, ALK+ NSCLC, Crizotinib

Blood First Assay Screening Trial (BFAST) in Treatment-Naive Advanced or Metastatic NSCLC: Initial Results of the Phase 2 ALK-Positive Cohort

Introduction: The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort. Conclusions: These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.07.008

Authors: Rafal Dziadziuszko, Tony Mok, Solange Peters, Ji-Youn Han, Jorge Alatorre-Alexander,
Natasha Leighl, Virote Sriuranpong, Maurice Pérol, Gilberto de Castro Junior, Ernest Nadal, Filippo de Marinis, Osvaldo Arén Frontera, Daniel S.W. Tan, Dae Ho Lee, Hye Ryun Kim, Mark Yan, Todd Riehl, Erica Schleifman, Sarah M. Paul, Simonetta Mocci, Rajesh Patel, Zoe June Assaf, David S. Shames, Michael S. Mathisen, Shirish M. Gadgeel

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

Pharmacometric analyses of alectinib to facilitate approval of the optimal dose for the first-line treatment of anaplastic lymphoma kinase–positive non-small cell lung cancer

Alectinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of ALK-positive non-small cell lung cancer. Population pharmacokinetic (PK) models were developed for alectinib and its major active metabolite M4 using phase I/II PK data in crizotinib-failed patients (N = 138). The PK profiles were best described by two separate models with similar structure for both entities: open one-compartment models with sequential zero/first-order input and first-order elimination rate. Body weight with fixed allometric scaling factor on clearance and volume of both entities was the only significant covariate. Bayesian feedback analyses of the PK data collected from Japanese and global treatment-naïve patients in phase III studies (N = 334) confirmed the body weight effect. Landmark Cox proportional hazards analyses of progression-free survival in treatment-naïve patients identified the average molar concentrations of both entities alectinib and M4 during the first 6 weeks of trea..... READ ARTICLE

CPT: Pharmacometrics & Systems Pharmacology DOI:10.1002/psp4.12702

Authors: Joy C. Hsu, Felix Jaminion, Elena Guerini, Bogdana Balas, Walter Bordogna, Peter N. Morcos, Nicolas Frey

Pre-Clinical, group3Kirk SmithSeptember 21, 2021Non-small cell lung cancer, ALK, Alectinib, Pharmacometric analyses, Optimal dose

Drug interaction profile of TKI alectinib allows effective and safe treatment of ALK+ lung cancer in the kidney transplant recipient

ALK targeting with tyrosine kinase inhibitors (TKIs) is a highly potent treatment option for the therapy of ALK positive non-small cell lung cancer (NSCLC). However, pharmacokinetics of TKIs leads to clinically significant drug interactions, and the interfering co-medication may hamper the anti-cancer therapeutic management. Here, we present for the first time a drug interaction profile of ALK-TKIs, crizotinib and alectinib, and immunosuppressive agent cyclosporine A in kidney transplant recipients diagnosed with ALK+ lung cancer.Based on therapeutic drug monitoring of cyclosporin A plasma level, the dose of cyclosporine A has been adjusted to achieve a safe and effective therapeutic level in terms of both cancer treatment and kidney transplant condition. Particularly, 15 years upon the kidney transplantation, the stage IV lung cancer patient was treated with the 1st-line chemotherapy, the 2nd-line ALK-TKI crizotinib followed by ALK-TKI alectinib. The successful therapy with ALK-TKIs h..... READ ARTICLE

International Immunopharmacology DOI:10.1016/j.intimp.2021.108012

Authors: Ondrej Bilek, Milos Holanek, Jan Jurica, Sona Stepankova, Jiri Vasina, Iveta Selingerova, Alexandr Poprach, Simona Borilova, Tomas Kazda, Igor Kiss, Lenka Zdrazilova-Dubska

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

Successful Alectinib Treatment for Carcinoma of Unknown Primary with EML4-ALK Fusion Gene: A Case Report

Gene alteration in anaplastic lymphoma kinase (ALK) is rare, and the efficacy of ALK inhibitors in the treatment of carcinoma of unknown primary (CUP) with ALK alteration remains unclear. The patient was a 56-year-old woman who presented with cervical lymph node swelling. Computed tomography revealed paraaortic, perigastric, and cervical lymph node swelling; ascites; a liver lesion; and a left adrenal mass. A cervical lymph node biopsy was performed, and pathological diagnosis of an undifferentiated malignant tumor was conducted. Finally, the patient was diagnosed with CUP and treated with chemotherapy. To evaluate actionable mutations, we performed a multigene analysis, using a next-generation sequencer (FoundationOne® CDx). It revealed that the tumor harbored an echinoderm microtubule-associated protein-like 4 (EML4) and ALK fusion gene. Additionally, immunohistochemistry confirmed ALK protein expression. Alectinib, a potent ALK inhibitor, was recommended for the patient at a molecular oncology conference at our institution. Accordingly, alectinib (600 mg/day) was administered, and the multiple lesions and symptoms rapidly diminished without apparent toxicity. The administration of alectinib continued for a period of 10 months without disease progression. Thus, ALK-tyrosine kinase inhibitors should be considered in patients with CUP harboring the EML4-ALK fusion gene. READ ARTICLE

Current Oncology DOI: 10.3390/curroncol28030180

Authors: Sugiyama K., Izumika A., Iwakoshi A., Nishibori R., Sato M., Shiraishi K., Hattori H., Nishimura R. and Kitagawa C.

Structure-based discovery of SIAIS001 as an oral bioavailability ALK degrader constructed from Alectinib

Fusion proteins of the anaplastic lymphoma kinase (ALK) are promising therapeutic targets for cancer and other human diseases, especially for non-small cell lung cancer (NSCLC) and anaplastic large-cell lymphomas (ALCLs). We described herein a structure-based design, synthesis, and evaluation of ALK PROTACs (proteolysis-targeting chimeras) based on Alectinib as the warhead. We firstly screened CRBN ligands as the E3 ligase moiety, then obtained a series of potent ALK degraders based on different CRBN ligands, exemplified by SIAIS091 and SIAIS001 with lenalidomide/thalidomide-based linkers. Both of them induced effective ALK degradation at low nanomolar concentrations in cells, and showed much better growth inhibition effects than Alectinib. SIAIS091 or SIAIS001 also promoted cell cycle arrest in G1/S phase. Finally, SIAIS001 exhibited good oral bioavailability in Pharmacokinetics study. READ ARTICLE

European Journal of Medicinal Chemistry DOI:10.1016/j.ejmech.2021.113335

Authors: Chaowei Ren, Ning Sun, Ying Kong, Xiaojuan Qu, Haixia Liu, Hui Zhong, Xiaoling Song, Xiaobao Yang, Biao Jiang

First Case Report of Pregnancy on Alectinib in a Woman With Metastatic ALK-Rearranged Lung Cancer: A Case Report

This is the first case report of a patient with ALK-rearranged metastatic lung adenocarcinoma who became pregnant during treatment with alectinib. A multidisciplinary team of gynecologists, neonatologists, oncologists, psychologists, and pharmacologists was set up to handle the case. According to patient’s preference, the study drug was continued throughout pregnancy and the woman delivered a healthy baby girl at 35 weeks and 5 days of gestation. Fetal parameters remained normal during pregnancy. At birth, alectinib levels were 14 times higher in maternal plasma than in the fetus (259 versus 18 ng/mL). The average concentration of alectinib in the placenta was 562 ng/g. The baby was followed during her first 20 months, and no developmental anomalies were observed. After 32 months from diagnosis, the mother is well and in partial remission. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.02.005

Authors: GiovannaScarfone, Monica Fumagalli, Martina Imbimbo, Tommaso Ceruti, Fulvia Milena Cribiù, Eugenia Di Loreto, Maurizio D’Incalci, Federica Facchin, Camilla Fontana, Marina C. Garassino, Fedro A. Peccatori, Nicola Persico, Diego Signorelli and Massimo Zucchetti

Case StudyKirk SmithMarch 30, 2021ALK rearrangement, Lung cancer, Alectinib, Pregnancy

Outcomes According to ALK Status Determined by Central Immunohistochemistry or Fluorescence In Situ Hybridization in Patients With ALK-Positive NSCLC Enrolled in the Phase 3 ALEX Study

Introduction: We retrospectively examined progression-free survival (PFS) and response by ALK fluorescence in situ hybridization (FISH) status in patients with advanced ALK immunohistochemistry (IHC)-positive NSCLC in the ALEX study. Conclusions: Outcomes of patients with ALK IHC-positive and FISH-positive and ALK IHC-positive and FISH-uninformative NSCLC were similar to those of the overall ALEX population. These results suggest that Ventana ALK IHC is a standard testing method for selecting patients for treatment with alectinib. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.10.007

Authors: Tony Mok, Solange Peters, Ross Camidge, Johannes Noé, Shirish Gadgeel, Sai-Hong Ignatius Ou, Dong-Wan Kim, Krzysztof Konopa, Emanuela Pozzi, Ting Liu, Isabell R. Loftin, Crystal Williams, Alice T. Shaw

Clinical TrialsKirk SmithFebruary 1, 2021Alectinib, ALK-positive, IHC, FISH, NSCLC

Combined small cell lung carcinoma harboring ALK rearrangement: A case report and literature review

Combined small cell lung cancer (c-SCLC) is a relatively rare subtype of SCLC and is defined by the combination of SCLC and any elements of non-small cell carcinoma (NSCLC). Standard chemotherapy for patients with c-SCLC has not yet been established. Gene mutations such as epidermal growth factor receptor (EGFR) mutations may be detected in patients with c-SCLC. However, little is known about ana-plastic lymphoma kinase (ALK) rearrangement in c-SCLC patients. Here, we report a young female patient who was successfully treated with alectinib for ALK-positive c-SCLC after failure of immunochemotherapy for SCLC and cytotoxic chemotherapy for adenocarcinoma. Moreover, we performed a literature review of EGFR- or ALK-positive c-SCLC patients. Our report suggests that ALK testing may be justified in patients with SCLC that contain an adenocarcinoma component READ ARTICLE

Thoracic Cancer DOI:10.1111/1759-7714.13716

Authors: Takayuki Niitsu, Takayuki Shiroyama, Kotaro Miyake, Yoshimi Noda, Kansuke Kido, Reina Hara,Takatoshi Enomoto, Yuichi Adachi, Saori Amiya,YasuhikoSuga, Kiyoharu Fukushima,Shohei Koyama, Kota Iwahori, Haruhiko Hirata, Izumi Nagatomo, Yoshito Takeda, Atsushi Kumanogoh

Case StudyKirk SmithOctober 25, 2020Alectinib, ALK, combined small cell carcinoma (c-SCLC), immunochemotherapy

Sustained Response to Crizotinib After Resistance to First-Line Alectinib Treatment in Two Patients With ALK-Rearranged NSCLC

... Here, we describe the sustained response to second-line crizotinib in two patients with echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged advanced NSCLC after failure of the first-line alectinib therapy with no secondary ALK mutations... We speculate that the sustained response to crizotinib in our cases was primarily owing to the absence of ALK resistance mutations. However, we cannot completely rule out the activation of other alternative pathways, as tumor rebiopsies were not performed after developing resistance to alectinib. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.01.003

Authors: Jing Zheng, Wenjia Sun, Wenhong Chen, Jianying Zhou, Jianya Zhou

Case StudyKirk SmithSeptember 1, 2020Crizotinib, Alectinib, ALK, NSCLC

Feasibility and Safety of Neoadjuvant Alectinib in a Patient With ALK-Positive Locally Advanced NSCLC

A 46-year-old man, a nonsmoker, was hospitalized owing to complaints of repeated cough and hemoptysis. Enhanced computed tomography scan revealed a large mass with a diameter of 66 mm located in the left lower lobe. Enlarged mediastinal lymph nodes were also identified with bulky station 7... Herein, we have first reported a clinically successful case involving neoadjuvant alectinib... Collectively, neoadjuvant alectinib may be clinically feasible and a registered real-world study will be set to further assess its clinical implication. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.12.133

Authors: Chao Zhang, Li-Xu Yan, Ben-Yuan Jiang, Yi-Long Wu, Wen-Zhao Zhong

Case StudyKirk SmithJune 1, 2020Neoadjuvant, Alectinib, ALK, NSCLC

Successful alectinib desensitization in a patient with anaplastic lymphoma kinase-positive adenocarcinoma of the lung and alectinib-induced drug rash

Alectinib is currently recommended as the preferred first-line treatment option for the treatment of metastatic anaplastic lymphoma kinase gene rearrangement-positive NSCLC due to improved progression-free survival when compared to crizotinib. The development of skin toxicity can lead to early discontinuation of alectinib treatment, forcing providers and patients to select alternative, potentially less effective options. This case report provides evidence that patients who have experienced severe skin toxicity due to alectinib may be able to continue this first-line treatment option by rechallenging them using a desensitization procedure. READ ARTICLE

Journal of Oncology Pharmacy Practice DOI:10.1177/1078155220918644

Authors: Anderson BE, Luczak TS, Ries LM, Hoefs GE, Silva-Benedict AC.

Case StudyKirk SmithMay 31, 2020Alectinib, desensitization, hypersensitivity, ALK-positive