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    Faculty & Disclosures
    Dr Andrew Wotherspoon

    Royal Marsden Hospital,
    London, UK

    Dr Andrew Wotherspoon is a consultant histopathologist at the Royal Marsden Hospital in London, UK, which is one of the largest cancer centres in Europe, a post he has held for 26 years. He is currently clinical lead for haematopathology. read more

    During his histopathology training, and subsequently as a diagnostic haematopathologist, Dr Wotherspoon developed an interest in the pathobiology of indolent lymphomas and chronic leukaemias. He has a particular interest in extranodal and splenic B-cell lymphoma and has made important contributions to the understanding of extranodal marginal zone lymphoma. After joining the Royal Marsden Hospital, he developed an additional special interest in the pathology of carcinoma of the digestive system.

    Dr Wotherspoon has authored over 330 research papers, 25 book chapters and three books. He has contributed to conferences and symposia in over 24 countries. He is currently past president of the European Association for Haematopathology. He has been a member of the council of the British Division of the International Academy of Pathology and is a member of the Medical Advisory Panel Lymphoma Action.

    Dr Andrew Wotherspoon has no financial interests/relationships or affiliations in relation to this activity.
    Dr Andrea Cercek

    Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Dr Andrea Cercek is a board-certified medical oncologist specializing in the treatment of patients with gastrointestinal (GI) cancers, particularly colorectal cancer (CRC), appendix cancer and cholangiocarcinoma.
    read more

    Dr Cercek is the founder and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer. This clinic, the first of its kind in the world, is dedicated solely to the specific needs of people under 50 years who have CRC or other GI cancers.

    Dr Cercek’s research is focused on the development of novel systemic and regional therapies, including approaches based on tumour genomics, with the goal of improving outcomes while minimizing treatment-related toxicities.

    Dr Andrea Cercek discloses: Advisory board/panel fees from Bayer, GlaxoSmithKline, Merck, Pfizer, Roche and Seagen. Grants/research support fees from GlaxoSmithKline and Seagen.
    Dr Elena Elez

    Vall d'Hebron University Hospital, Barcelona, Spain

    Dr Elena Elez is a medical oncology consultant at Vall d’Hebron University Hospital and a senior investigator at Vall d’Hebron Institute of Oncology (VHIO). read more

    Since her appointment in 2007, Dr Elez has participated as principal investigator and sub-investigator in many clinical trials with molecular therapy primarily directed to the signalling pathway of the MAP kinases in metastatic colorectal cancer (CRC). The results of this research have been crucial for the consolidation of the VHIO’s Gastrointestinal and Endocrine Tumors Group as a reference in the CRC research field, enabling the leadership of one of the most relevant collaborative clinical projects in oncology at European level.

    Dr Elez has played a key role in the development of a research programme in the mutated BRAF CRC patient population. The results of this research have been highly productive, leading to a number of publications in journals such as Nature Medicine and The New England Journal of Medicine. She is also involved in international collaborative projects focused on translational research in CRC in areas such as liquid biopsy and the microbiome, among others. Dr Elez is particularly involved in training and education and leads the young oncologists section at the Spanish Society of Medical Oncology and chairs the VHIO educational programme.

    Dr Elena Elez discloses: Advisory board/panel fees from Amgen, Bayer, Hoffmann-La Roche, Merck Serono, MSD, Novartis, Organon, Pierre Fabre, Sanofi, Seagen and Servier. Other financial or material support from Amgen, Array BioPharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Debiopharm, Genentech, HalioDX, Hoffmann-La Roche, Hutchison MediPharma, Janssen, MedImmune, Menarini, Merck, MSD, Merus, Mirati Therapeutics, Novartis, Pfizer, PharmaMar, Sanofi, Servier and Taiho Pharma.
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    Fulfilling the potential of HER2-targeting in colorectal cancer: An update on detection and management

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    Dr Andrew Wotherspoon is a consultant histopathologist at the Royal Marsden Hospital in London, UK, which is one of the largest cancer centres in Europe, a post he has held for 26 years. He is currently clinical lead for haematopathology. read more

    During his histopathology training, and subsequently as a diagnostic haematopathologist, Dr Wotherspoon developed an interest in the pathobiology of indolent lymphomas and chronic leukaemias. He has a particular interest in extranodal and splenic B-cell lymphoma and has made important contributions to the understanding of extranodal marginal zone lymphoma. After joining the Royal Marsden Hospital, he developed an additional special interest in the pathology of carcinoma of the digestive system.

    Dr Wotherspoon has authored over 330 research papers, 25 book chapters and three books. He has contributed to conferences and symposia in over 24 countries. He is currently past president of the European Association for Haematopathology. He has been a member of the council of the British Division of the International Academy of Pathology and is a member of the Medical Advisory Panel Lymphoma Action.

    Dr Andrew Wotherspoon has no financial interests/relationships or affiliations in relation to this activity.

    Take CE/CME Test

    Dr Andrea Cercek is a board-certified medical oncologist specializing in the treatment of patients with gastrointestinal (GI) cancers, particularly colorectal cancer (CRC), appendix cancer and cholangiocarcinoma. read more

    Dr Cercek is the founder and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer. This clinic, the first of its kind in the world, is dedicated solely to the specific needs of people under 50 years who have CRC or other GI cancers.

    Dr Cercek’s research is focused on the development of novel systemic and regional therapies, including approaches based on tumour genomics, with the goal of improving outcomes while minimizing treatment-related toxicities.

    Dr Andrea Cercek discloses: Advisory board/panel fees from Bayer, GlaxoSmithKline, Merck, Pfizer, Roche and Seagen. Grants/research support fees from GlaxoSmithKline and Seagen.

    Take CE/CME Test

    Dr Elena Elez is a medical oncology consultant at Vall d’Hebron University Hospital and a senior investigator at Vall d’Hebron Institute of Oncology (VHIO). read more

    Since her appointment in 2007, Dr Elez has participated as principal investigator and sub-investigator in many clinical trials with molecular therapy primarily directed to the signalling pathway of the MAP kinases in metastatic colorectal cancer (CRC). The results of this research have been crucial for the consolidation of the VHIO’s Gastrointestinal and Endocrine Tumors Group as a reference in the CRC research field, enabling the leadership of one of the most relevant collaborative clinical projects in oncology at European level.

    Dr Elez has played a key role in the development of a research programme in the mutated BRAF CRC patient population. The results of this research have been highly productive, leading to a number of publications in journals such as Nature Medicine and The New England Journal of Medicine. She is also involved in international collaborative projects focused on translational research in CRC in areas such as liquid biopsy and the microbiome, among others. Dr Elez is particularly involved in training and education and leads the young oncologists section at the Spanish Society of Medical Oncology and chairs the VHIO educational programme.

    Dr Elena Elez discloses: Advisory board/panel fees from Amgen, Bayer, Hoffmann-La Roche, Merck Serono, MSD, Novartis, Organon, Pierre Fabre, Sanofi, Seagen and Servier. Other financial or material support from Amgen, Array BioPharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Debiopharm, Genentech, HalioDX, Hoffmann-La Roche, Hutchison MediPharma, Janssen, MedImmune, Menarini, Merck, MSD, Merus, Mirati Therapeutics, Novartis, Pfizer, PharmaMar, Sanofi, Servier and Taiho Pharma.

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    Useful tips
    • Downloads including slides are available for this activity in the Toolkit
    Learning Objectives

    After watching this activity, participants should be better able to:

    • Discuss the importance of and approaches for detecting HER2 amplifications in patients with CRC
    • Summarize clinical efficacy data for guideline-recommended HER2-targeted treatments for patients with mCRC
    • Appraise investigational evidence and future perspectives for emerging HER2-targeting approaches in HER2-amplified CRC
    Overview

    In this activity, three experts provide their insights on detection methods for HER2 amplification, as well as the clinical efficacy data for guideline-recommended HER2-targeted therapies and emerging HER2-targeted therapies for patients with mCRC.

    This activity is jointly provided by USF Health and touchIME. read more

    Target Audience

    Oncologists and gastrointestinal oncologists, pathologists and oncology nurses involved in the management of patients with CRC.

    Disclosures

    USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

    Faculty

    Dr Andrew Wotherspoon has no financial interests/relationships or affiliations in relation to this activity.

    Dr Andrea Cercek discloses: Advisory board/panel fees from Bayer, GlaxoSmithKline, Merck, Pfizer, Roche and Seagen. Grants/research support fees from GlaxoSmithKline and Seagen.

    Dr Elena Elez discloses: Advisory board/panel fees from Amgen, Bayer, Hoffmann-La Roche, Merck Serono, MSD, Novartis, Organon, Pierre Fabre, Sanofi, Seagen and Servier. Other financial or material support from Amgen, Array BioPharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Debiopharm, Genentech, HalioDX, Hoffmann-La Roche, Hutchison MediPharma, Janssen, MedImmune, Menarini, Merck, MSD, Merus, Mirati Therapeutics, Novartis, Pfizer, PharmaMar, Sanofi, Servier and Taiho Pharma.

    Content reviewer

    Bailey Blankenship, APRN, has no financial interests/relationships or affiliations in relation to this activity.

    Touch Medical Director

    Sadaf Kazi has no financial interests/relationships or affiliations in relation to this activity.

    USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

    Requirements for Successful Completion

    In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

    If you have questions regarding credit please contact cpdsupport@usf.edu.

    Accreditations

    Physicians

    This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

    USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

    Advanced Practice Providers

    Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

    The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

    Nurses

    USF Health is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation.

    A maximum of 0.75 contact hours may be earned by learners who successfully complete this continuing professional development activity. USF Health, the accredited provider, acknowledges touchIME as the joint provider in the planning and execution of this CNE activity.

    This activity is awarded 0.75 ANCC pharmacotherapeutic contact hour.

    Date of original release: 27 July 2023. Date credits expire: 27 July 2024.

    If you have any questions regarding credit please contact cpdsupport@usf.edu.

    This activity is CE/CME accredited

    To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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    Topics covered in this activity

    Colorectal Cancer / Gastrointestinal Cancers
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    This Activity Is Funded By:

    An independent medical education grant from Seagen Inc.
    This activity is jointly provided by USF Health and touchIME.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals.

    Date of original release: 27 July 2023. Date credits expire: 27 July 2024.

    Claim Credit
    touchEXPERT OPINIONS
    Fulfilling the potential of HER2-targeting in colorectal cancer: An update on detection and management
    0.75 CE/CME credit
    Question 1/5
    HER2 testing is carried out via immunohistochemistry on your 55-year-old female patient with mCRC. What is the range of HER2 scoring used with this method?

    HER2, human epidermal growth factor receptor 2; mCRC, metastatic colorectal cancer.

    The expression of HER2 in CRC can be evaluated by using immunohistochemistry and is based on the pattern and intensity of membranous reactivity and the percentage of immunoreactive cells. Both circumferential and basolateral/lateral patterns are considered, and the scoring ranges from 0 to 3+.

    Abbreviations

    CRC, colorectal cancer; HER2, human epidermal growth factor receptor 2.

    Reference

    Ivanova M, et al. Life. 2022;12:1403.

    Question 2/5
    In the phase IIa MyPathway trial, what was the ORR for patients with HER2-positive mCRC who were treated with trastuzumab plus pertuzumab?

    HER2, human epidermal growth factor receptor 2; mCRC, metastatic colorectal cancer; ORR, overall response rate.

    In the phase IIa MyPathway trial, an ORR of 32% was reported in 57 patients with HER2-amplified mCRC treated with pertuzumab (840 mg IV loading dose, followed by 420 mg given by IV every 3 weeks) and trastuzumab (8 mg/kg IV loading dose, followed by 6 mg/kg given by IV every 3 weeks).

    Abbreviations

    HER2, human epidermal growth factor receptor 2; IV, intravenous; mCRC, metastatic colorectal cancer; ORR, overall response rate.

    Reference

    Meric-Bernstam F, et al. Lancet Oncol. 2019;20:518–30.

    Question 3/5
    Your patient has HER2-amplified, RAS and BRAF wild-type mCRC that has progressed following capecitabine and oxaliplatin-based chemotherapy. Based on the 2023 NCCN guidelines, which of the following would you consider as a subsequent therapy option?

    BRAF, v-Raf murine sarcoma viral oncogene homolog B1; HER2, human epidermal growth factor receptor 2; mCRC, metastatic colorectal cancer; NCCN, National Comprehensive Cancer Network; RAS, rat sarcoma virus.

    According to the 2023 NCCN guidelines, trastuzumab + [lapatinib, pertuzumab or tucatinib] or trastuzumab deruxtecan can be considered for patients with HER2-amplified, RAS and BRAF wild-type, advanced or mCRC that has progressed following fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy.1,2

    There has been low activity of HER2-directed monotherapy observed in preclinical studies.3 The 2023 NCCN guidelines recommend four different regimens as options for subsequent treatment of mCRC with HER2 amplifications: trastuzumab deruxtecan monotherapy or trastuzumab in combination with pertuzumab, lapatinib, or tucatinib. Tucatinib monotherapy or trastuzumab monotherapy are not recommended.1,2

    Neratinib is not currently approved to treat CRC, but is under investigation as a HER2-targeted CRC therapy option.4

    Abbreviations

    BRAF, v-Raf murine sarcoma viral oncogene homolog B1; CRC, colorectal cancer; HER2, human epidermal growth factor receptor 2; mCRC, metastatic CRC; NCCN, National Comprehensive Cancer Network; RAS, rat sarcoma virus.

    References

    1. NCCN. Colon cancer. Version 2.2023. Available at: www.nccn.org/professionals/physician_gls/pdf/colon.pdf (accessed 28 June 2023).
    2. NCCN. Rectal cancer. Version 3.2023. Available at: www.nccn.org/professionals/physician_gls/pdf/rectal.pdf (accessed 28 June 2023).
    3. Strickler JH, et al. Lancet Oncol. 2023;24:496–508.
    4. Jacobs SA, et al. J Clin Oncol. 2022;40(Suppl.):3564.
    Question 4/5
    When treating patients with trastuzumab and pertuzumab as part of the phase II TRIUMPH trial, which of the following would you expect to see in patients with mCRC tested for HER2 by ctDNA genotyping or conventional tumour tissue analysis?

    ctDNA, circulating tumour DNA; HER2, human epidermal growth factor receptor 2; mCRC, metastatic colorectal cancer.

    The TRIUMPH phase II clinical trial evaluated the efficacy of trastuzumab plus pertuzumab in patients with mCRC with RAS wild-type and HER2 amplification prospectively confirmed by tumour tissue or ctDNA analysis. It concluded that patients with HER2-amplified mCRC identified by ctDNA genotyping benefited from dual-HER2 blockade similarly to patients identified by conventional tissue analysis.

    Abbreviations

    ctDNA, circulating tumour DNA; HER2, human epidermal growth factor receptor 2; mCRC, metastatic colorectal cancer; RAS, rat sarcoma virus.

    Reference

    Nakamura Y, et al. Nat Med. 2021;27:1899–903.

    Question 5/5
    Your patient has mCRC and you decide to test for HER2. The test results show that the tumour has HER2 amplification and not HER2 mutation. Based on findings from the TAPUR trial, what would you recommend as an appropriate treatment option and why?

    HER2, human epidermal growth factor receptor 2; mCRC, metastatic colorectal cancer.

    The phase II TAPUR study evaluated antitumour activity of available targeted agents in patients with advanced cancers harbouring potentially actionable genomic alterations. Two cohorts of patients with mCRC with either HER2 amplifications or HER2/3 mutations treated with trastuzumab + pertuzumab were reported. The study found that trastuzumab + pertuzumab treatment does not appear to have antitumour activity in patients with mCRC with HER2/3 mutations, but did have antitumour activity in patients with mCRC with HER2 amplification.

    Abbreviations

    HER2/3, human epidermal growth factor receptor 2/3; mCRC, metastatic colorectal cancer.

    Reference

    Gupta R, et al. JCO Precis Oncol. 2022;6:e2200306.

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    This Activity Is Funded By:

    An independent medical education grant from Seagen Inc.
    This activity is jointly provided by USF Health and touchIME.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals.

    Date of original release: 27 July 2023. Date credits expire: 27 July 2024.

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