Cotellic, INN-Cobimetinib
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Oncofocus® Precision Oncology
Medical Laboratory Accredited to ISO15189:2012 Oncofocus® Precision Oncology ONCOFOCUS® TEST REPORT Oncologica UK Ltd Suite 15-16, The Science Village Chesterford Research Park Cambridge, CB10 1XL, UK Tel: +44(0)1223 785327 Email: [email protected] Lead Clinical Scientist: - Pre-Reg Clinical Scientist: - Date: 1 of 30 ONC19 - Surname - Requester - Forename - Contact details - DOB - Date requested - Gender - Histology # - Tumour % - Primary site Breast Tumour % - Tumour subtype - (macrodissected) Tissue Type - Comment: The DNA and RNA extracted from this sample were of optimal quality. The Oncofocus assay on which the sample was run met all assay specific quality metrics. Oncofocus currently targets 505 genes covering oncogenes, fusion genes, genes susceptible to copy number variation and tumour suppressors. Actionable genetic variants detected by Oncofocus are currently linked to 687 anti-cancer targeted therapies/therapy combinations. The following actionable variants were detected: Within the 'Current Clinical Trials Information' section of this report, starting on page 8, the NCT numbers are hyperlinks to the clinicaltrials.gov webpages which should be accessed to gain further trial specific information Sample Cancer Type: Breast Cancer Clinically Significant Biomarkers Indicated Contraindicated Relevant Therapies Relevant Therapies Genomic Alteration Alt allele freq (In this cancer type) (In other cancer type) Clinical Trials ERBB2 p.(G727A) c.2180G>C 39% Clinical trials and/or off-label ado-trastuzumab emtansine 19 BRAF p.(V600E) c.1799T>A 5% Clinical trials and/or off-label dabrafenib 13 vemurafenib PIK3CA p.(G1049R) c.3145G>C 58% Clinical trials and/or off-label Clinical trials and/or off-label 15 Sources included in relevant therapies: EMA1, FDA2, ESMO, NCCN Hotspot variants with >10% alternate allele reads are classified as ‘detected’ with an assay sensitivity and positive predictive value(PPV) of 99%. -
Product Monograph Including Patient Medication Information
PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION Pr ® COTELLIC cobimetinib tablets 20 mg cobimetinib (as cobimetinib fumarate) Protein Kinase Inhibitor Date of Revision: Hoffmann-La Roche Limited January 5, 2018 7070 Mississauga Road Mississauga, Ontario, Canada L5N 5M8 www.rochecanada.com Submission Control No: 209926 COTELLIC®, ZELBORAF® are registered trade-marks of F. Hoffmann-La Roche AG, used under license ©Copyright 2016-2017, Hoffmann-La Roche Limited Page 1 of 38 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION .........................................................3 SUMMARY PRODUCT INFORMATION ........................................................................3 INDICATIONS AND CLINICAL USE ..............................................................................3 CONTRAINDICATIONS ...................................................................................................3 WARNINGS AND PRECAUTIONS ..................................................................................4 ADVERSE REACTIONS ..................................................................................................11 DRUG INTERACTIONS ..................................................................................................15 DOSAGE AND ADMINISTRATION ..............................................................................17 OVERDOSAGE ................................................................................................................20 ACTION AND CLINICAL PHARMACOLOGY ............................................................20 -
Quantification of Cobimetinib, Cabozantinib, Dabrafenib, Niraparib
University of Groningen Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC-MS/MS Krens, Stefanie D; van der Meulen, Eric; Jansman, Frank G A; Burger, David M; van Erp, Nielka P Published in: Biomedical chromatography DOI: 10.1002/bmc.4758 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2020 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Krens, S. D., van der Meulen, E., Jansman, F. G. A., Burger, D. M., & van Erp, N. P. (2020). Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC-MS/MS. Biomedical chromatography, 34(3), [4758]. https://doi.org/10.1002/bmc.4758 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. -
New Oncology Reimbursements in Belgium
33 New oncology reimbursements in Belgium P. Specenier, MD, PhD OVERVIEW OF BELGIAN REIMBURSEMENT NEWS (BELG J MED ONCOL 2018;12(1):33-34) TEMOZOLOMIDE® (TEMODAR/TEMODAL) was 7.4 months (95% confidence interval [CI] 5.6-9.1) with Some companies have transferred temozolomide from chap- cabozantinib versus 3.8 months (95% CI 3.7-5.4) with ever- ter IV to chapter I. These can now be prescribed without re- olimus with a hazard ratio (HR) of 0.58 (95% CI 0.45-0.74; strictions. In the near future, other temozolomide brands are p<0.0001). Similar data were observed in the intent-to-treat also expected to be transferred. population. A planned interim analysis of overall survival (OS) was conducted at the time of the PFS analysis and did LOMUSTINE (CCNU) not reach the interim boundary for statistical significance The reimbursement criteria for lomustine have been modi- (HR=0.68 [0.51, 0.90], p=0.006). However, in a subsequent fied and are entirely concordant with the recently modified unplanned interim analysis of OS, a statistically significant criteria for procarbazine, except for the indication Hodgkin’s improvement was demonstrated (median 21.4 months ver- disease, which only applies for procarbazine. sus 16.5 months; HR=0.66; 95% CI 0.53-0.83; p=0.0003). The overall response rate (ORR) was 17% (95% CI 13-22) for CABOMETYX® (CABOZANTINIB) cabozantinib and 3% (95% CI 2-6) for everolimus (p<0.0001). Cabometyx® (cabozantinib) can be reimbursed for patients with advanced renal cell carcinoma (RCC) after at least one COTELLIC® (COBIMETINIB) prior anti-VEGF directed agent. -
Combined BRAF and MEK Inhibition with Vemurafenib and Cobimetinib for Patients with Advanced Melanoma
Review Melanoma Combined BRAF and MEK Inhibition with Vemurafenib and Cobimetinib for Patients with Advanced Melanoma Antonio M Grimaldi, Ester Simeone, Lucia Festino, Vito Vanella and Paolo A Ascierto Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione “G. Pascale”, Napoli, Italy cquired resistance is the most common cause of BRAF inhibitor monotherapy treatment failure, with the majority of patients experiencing disease progression with a median progression-free survival of 6-8 months. As such, there has been considerable A focus on combined therapy with dual BRAF and MEK inhibition as a means to improve outcomes compared with monotherapy. In the COMBI-d and COMBI-v trials, combined dabrafenib and trametinib was associated with significant improvements in outcomes compared with dabrafenib or vemurafenib monotherapy, in patients with BRAF-mutant metastatic melanoma. The combination of vemurafenib and cobimetinib has also been investigated. In the phase III CoBRIM study in patients with unresectable stage III-IV BRAF-mutant melanoma, treatment with vemurafenib and cobimetinib resulted in significantly longer progression-free survival and overall survival (OS) compared with vemurafenib alone. One-year OS was 74.5% in the vemurafenib and cobimetinib group and 63.8% in the vemurafenib group, while 2-year OS rates were 48.3% and 38.0%, respectively. The combination was also well tolerated, with a lower incidence of cutaneous squamous-cell carcinoma and keratoacanthoma compared with monotherapy. Dual inhibition of both MEK and BRAF appears to provide a more potent and durable anti-tumour effect than BRAF monotherapy, helping to prevent acquired resistance as well as decreasing adverse events related to BRAF inhibitor-induced activation of the MAPK-pathway. -
Dangerous Liaisons: Flirtations Between Oncogenic BRAF and GRP78 in Drug-Resistant Melanomas
Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug-resistant melanomas Shirish Shenolikar J Clin Invest. 2014;124(3):973-976. https://doi.org/10.1172/JCI74609. Commentary BRAF mutations in aggressive melanomas result in kinase activation. BRAF inhibitors reduce BRAFV600E tumors, but rapid resistance follows. In this issue of the JCI, Ma and colleagues report that vemurafenib activates ER stress and autophagy in BRAFV600E melanoma cells, through sequestration of the ER chaperone GRP78 by the mutant BRAF and subsequent PERK activation. In preclinical studies, treating vemurafenib-resistant melanoma with a combination of vemurafenib and an autophagy inhibitor reduced tumor load. Further work is needed to establish clinical relevance of this resistance mechanism and demonstrate efficacy of autophagy and kinase inhibitor combinations in melanoma treatment. Find the latest version: https://jci.me/74609/pdf commentaries F2-2012–279017) and NEUROKINE net- from the brain maintains CNS immune tolerance. 17. Benner EJ, et al. Protective astrogenesis from the J Clin Invest. 2014;124(3):1228–1241. SVZ niche after injury is controlled by Notch mod- work (EU Framework 7 ITN project). 8. Sawamoto K, et al. New neurons follow the flow ulator Thbs4. Nature. 2013;497(7449):369–373. of cerebrospinal fluid in the adult brain. Science. 18. Sabelstrom H, et al. Resident neural stem cells Address correspondence to: Gianvito Mar- 2006;311(5761):629–632. restrict tissue damage and neuronal loss after spinal tino, Neuroimmunology Unit, Institute 9. Butti E, et al. Subventricular zone neural progeni- cord injury in mice. Science. 2013;342(6158):637–640. tors protect striatal neurons from glutamatergic 19. -
Preferential Response of Basal-Like Head and Neck Squamous Cell Carcinoma Cell Lines to EGFR-Targeted Therapy Depending on EREG-Driven Oncogenic Addiction
Article Preferential Response of Basal-Like Head and Neck Squamous Cell Carcinoma Cell Lines to EGFR-Targeted Therapy Depending on EREG-Driven Oncogenic Addiction Sylvie Job 1, Aurélien de Reyniès 1, Betty Heller 2, Amélie Weiss 2, Eric Guérin 3,4, Christine Macabre 4,5, Sonia Ledrappier 4,5, Cyril Bour 4,5, Christine Wasylyk 2, Nelly Etienne-Selloum 5,6, Laurent Brino 2, Christian Gaiddon 4, Bohdan Wasylyk 2,† and Alain C. Jung 4,5,†,* 1 Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, 75013 Paris, France; [email protected] (S.J.); [email protected] (A.d.R.) 2 Institut de Génétique et de Biologie Moléculaire et Cellulaire IGBMC, UMR 7104 CNRS-UdS, U.1258 INSERM, 1 rue Laurent Fries, BP 10142, 67404 Illkirch cedex, France.; [email protected] (B.H.); [email protected] (A.W.); [email protected] (C.W.); [email protected] (L.B.); [email protected] (B.W.) 3 Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, 67098 Strasbourg, France; [email protected] 4 Université de Strasbourg, Inserm, UMR_S1113, 67200 Strasbourg, France; [email protected] (C.M.); [email protected] (S.L.); [email protected] (C.B.); [email protected] (C.G.) 5 Centre de Lutte Contre le Cancer Paul Strauss, 67000 Strasbourg, France; [email protected] 6 UMR 7021 CNRS/Unistra, Laboratoire de Bioimagerie et Pathologies (LBP), Faculté de Pharmacie, 67401 Illkirch, France * Correspondence: [email protected]; Tel.: +33-0388275367 † These authors contributed equally to this work. -
Darkening and Eruptive Nevi During Treatment with Erlotinib
CASE LETTER Darkening and Eruptive Nevi During Treatment With Erlotinib Stephen Hemperly, DO; Tanya Ermolovich, DO; Nektarios I. Lountzis, MD; Hina A. Sheikh, MD; Stephen M. Purcell, DO A 70-year-old man with NSCLCA presented with PRACTICE POINTS eruptive nevi and darkening of existing nevi 3 months after • Cutaneous side effects of erlotinib include acneform starting monotherapy with erlotinib. Physical examina- eruption, xerosis, paronychia, and pruritus. tion demonstrated the simultaneous appearance of scat- • Clinicians should monitor patients for darkening tered acneform papules and pustules; diffuse xerosis; and and/or eruptive nevi as well as melanoma during numerous dark copybrown to black nevi on the trunk, arms, treatment with erlotinib. and legs. Compared to prior clinical photographs taken in our office, darkening of existing medium brown nevi was noted, and new nevi developed in areas where no prior nevi had been visible (Figure 1). To the Editor: notThe patient’s medical history included 3 invasive mel- Erlotinib is a small-molecule selective tyrosine kinase anomas, all of which were diagnosed at least 7 years prior inhibitor that functions by blocking the intracellular por- to the initiation of erlotinib and were treated by surgical tion of the epidermal growth factor receptor (EGFR)Do1,2; excision alone. Prior treatment of NSCLCA consisted of a EGFR normally is expressed in the basal layer of the left lower lobectomy followed by docetaxel, carboplatin, epidermis, sweat glands, and hair follicles, and is over- pegfilgrastim, dexamethasone, and pemetrexed. A thor- expressed in some cancers.1,3 Normal activation of ough review of all of the patient’s medications revealed EGFR leads to signal transduction through the mitogen- no associations with changes in nevi. -
FOI Reference: FOI 414 - 2021
FOI Reference: FOI 414 - 2021 Title: Researching the Incidence and Treatment of Melanoma and Breast Cancer Date: February 2021 FOI Category: Pharmacy FOI Request: 1. How many patients are currently (in the past 3 months) undergoing treatment for melanoma, and how many of these are BRAF+? 2. In the past 3 months, how many melanoma patients (any stage) were treated with the following: • Cobimetinib • Dabrafenib • Dabrafenib AND Trametinib • Encorafenib AND Binimetinib • Ipilimumab • Ipilimumab AND Nivolumab • Nivolumab • Pembrolizumab • Trametinib • Vemurafenib • Vemurafenib AND Cobimetinib • Other active systemic anti-cancer therapy • Palliative care only 3. If possible, could you please provide the patients treated in the past 3 months with the following therapies for metastatic melanoma ONLY: • Ipilimumab • Ipilimumab AND Nivolumab • Nivolumab • Pembrolizumab • Any other therapies 4. In the past 3 months how many patients were treated with the following for breast cancer? • Abemaciclib + Anastrozole/Exemestane/Letrozole • Abemaciclib + Fulvestrant • Alpelisib + Fulvestrant • Atezolizumab • Bevacizumab [Type text] • Eribulin • Everolimus + Exemestane • Fulvestrant as a single agent • Gemcitabine + Paclitaxel • Lapatinib • Neratinib • Olaparib • Palbociclib + Anastrozole/Exemestane/Letrozole • Palbociclib + Fulvestrant • Pertuzumab + Trastuzumab + Docetaxel • Ribociclib + Anastrozole/Exemestane/Letrozole • Ribociclib + Fulvestrant • Talazoparib • Transtuzumab + Paclitaxel • Transtuzumab as a single agent • Trastuzumab emtansine • Any other -
Cobimetinib/Vemurafenib Combination Therapy for Melanoma: a Nursing Tool from the Melanoma Nursing Initiative (MNI)
Cobimetinib/Vemurafenib Combination Therapy for Melanoma: A Nursing Tool From The Melanoma Nursing Initiative (MNI) Cobimetinib (Cotellic®)/vemurafenib (Zelboraf®) combination therapy is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. Cobimetinib is a MEK1 and MEK2 inhibitor, and vemurafenib is an inhibitor of some mutated forms of BRAF kinase, including BRAF V600E. About half of patients with melanoma have a mutated form of the BRAF protein in their tumors. Combination MEK/ BRAF inhibitor therapy is associated with superior tumor response and improved patient survival compared with single-agent BRAF inhibitor therapy. Using the combination also decreases the high rates of secondary cutaneous malignancies associated with single-agent BRAF inhibitory therapy. This document is part of an overall nursing toolkit intended to assist nurses in optimizing care of melanoma patients receiving newer anti-melanoma therapies. © 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org Inspired By Patients . Empowered By Knowledge . Impacting Melanoma DRUG-DOSING/ADMINISTRATION • For advanced melanoma, both cobimetinib and vemurafenib are orally administered drugs. Cobimetinib is administered as 60 mg (three 20-mg tablets) once daily for 3 weeks, followed by a 1-week break, and vemurafenib as 960 mg (four 240-mg tablets) twice daily, for a total daily dosage of 1920 mg, each according to the regimens outlined below. The cobimetinib dose can be taken at the same time as one of the vemurafenib doses. The schedule repeats until disease progression or unacceptable toxicity occurs. • If the patient misses a dose of cobimetinib or vemurafenib, adjust as follows: » Cobimetinib: If ≤4 hours from scheduled dosing time, take the dose. -
New Century Health Policy Changes April 2021
Policy # Drug(s) Type of Change Brief Description of Policy Change new Pepaxto (melphalan flufenamide) n/a n/a new Fotivda (tivozanib) n/a n/a new Cosela (trilaciclib) n/a n/a Add inclusion criteria: NSCLC UM ONC_1089 Libtayo (cemiplimab‐rwlc) Negative change 2.Libtayo (cemiplimab) may be used as montherapy in members with locally advanced, recurrent/metastatic NSCLC, with PD‐L1 ≥ 50%, negative for actionable molecular markers (ALK, EGFR, or ROS‐1) Add inclusion criteria: a.As a part of primary/de�ni�ve/cura�ve‐intent concurrent chemo radia�on (Erbitux + Radia�on) as a single agent for members with a UM ONC_1133 Erbitux (Cetuximab) Positive change contraindication and/or intolerance to cisplatin use OR B.Head and Neck Cancers ‐ For recurrent/metasta�c disease as a single agent, or in combination with chemotherapy. Add inclusion criteria: UM ONC_1133 Erbitux (Cetuximab) Negative change NOTE: Erbitux (cetuximab) + Braftovi (encorafenib) is NCH preferred L1 pathway for second‐line or subsequent therapy in the metastatic setting, for BRAFV600E positive colorectal cancer.. Add inclusion criteria: B.HER‐2 Posi�ve Breast Cancer i.Note #1: For adjuvant (post‐opera�ve) use in members who did not receive neoadjuvant therapy/received neoadjuvant therapy and did not have any residual disease in the breast and/or axillary lymph nodes, Perjeta (pertuzumab) use is restricted to node positive stage II and III disease only. ii.Note #2: Perjeta (pertuzumab) use in the neoadjuvant (pre‐opera�ve) se�ng requires radiographic (e.g., breast MRI, CT) and/or pathologic confirmation of ipsilateral (same side) axillary nodal involvement. -
Trastuzumab Emtansine (T-DM1) and Stereotactic Radiation in the Management of HER2+ Breast Cancer Brain Metastases Matthew N
Mills et al. BMC Cancer (2021) 21:223 https://doi.org/10.1186/s12885-021-07971-w RESEARCH ARTICLE Open Access Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases Matthew N. Mills1* , Chelsea Walker2, Chetna Thawani2, Afrin Naz2, Nicholas B. Figura1, Sergiy Kushchayev3, Arnold Etame4, Hsiang-Hsuan Michael Yu1, Timothy J. Robinson1, James Liu4, Michael A. Vogelbaum4, Peter A. Forsyth4, Brian J. Czerniecki5, Hatem H. Soliman5, Hyo S. Han5 and Kamran A. Ahmed1 Abstract Background: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation. Methods: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging. Results: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14–24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%).