touchPANEL DISCUSSION

Optimizing strategies for the treatment of colorectal cancer in the biomarker era

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    Faculty & Disclosures
    Dr Kei Muro

    Aichi Cancer Center Hospital, Nagoya, Japan

    Dr Kei Muro, MD, PhD, is chief and director of the Department of Clinical Oncology and Outpatient Treatment Center at Aichi Cancer Center Hospital in Nagoya, Japan. read more

    He is an adjunct professor at Nagoya University Graduate School of Medicine and Tokyo University Graduate School of Medical Science, and is an adjunct and clinical professor at Nagoya City University Graduate School of Medical Science.

    Dr Muro graduated from the University of Tohoku Medical School in 1990 and completed his internal medicine training at the Iwaki Kyoritsu Hospital in 1993. He completed his residency in gastrointestinal oncology in the Digestive Endoscopy Division at the National Cancer Center Hospital East in 1997 and has been a staff doctor in the Gastrointestinal Oncology Division at the National Cancer Center Hospital since 1997. He was awarded his PhD in medical science from the Yokohama City University in 2021.

    Dr Muro is an executive board member of the Japanese Society of Medical Oncology and the Japanese Gastric Cancer Association. He is also a council member of the Japan Esophageal Society and the Japanese Cancer Association. He is a member of the American Society of Clinical Oncology and was a faculty member of the gastrointestinal tumours group at the European Society of Medical Oncology (2017–2021). He collaborates with the World Health Organization on the Japanese Gastric Cancer Committee. In terms of clinical trial activity, he is the chair of the gastrointestinal cancer group in the West Japan Oncology Group. He is also a reviewer for the Japanese Journal of Clinical Oncology and Esophagus. Furthermore, he was awarded the Nagoya International Cancer Treatment Symposium BMS Award in 2012 and was also awarded the Excellent Presentation Award from the Japan Society of Clinical Oncology in 2013. He is the author of more than 370 peer-reviewed publications.

    Dr Kei Muro discloses: Advisory board or panel fees from Amgen and AstraZeneca. Consultancy fees from Chugai and Ono. Grants/research support from Amgen, Astellas, Daiichi Sankyo, Eisai, Merck Serono, MSD, Novartis, Ono, Parexel International, Pfizer, Sanofi, Solasia Pharma and Taiho. Speaker’s bureau fees from Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Ono and Taiho.
    Dr Rachel Riechelmann

    AC Camargo Cancer Center, São Paulo, Brazil

    Prof. Rachel Riechelmann, MD, PhD, is a medical oncologist and clinical scientist specializing in colorectal and anal cancers and neuroendocrine tumours (NET). She is currently the director of the Clinical Oncology Department at the AC Camargo Cancer Center in São Paulo, Brazil, and also serves as the president of the Brazilian Gastrointestinal Tumors Group (GTG). read more

    She has published more than 125 articles in peer-reviewed journals and is editor of Methods and Biostatistics in Oncology: Understanding Clinical Research as an Applied Tool (Springer, 2018). Prof. Riechelmann is a member of two European Society of Medical Oncology scientific committees (colorectal and NET), the Latin American Society of GI Oncology (SLAGO) and the European Society of Neuroendocrine Tumors Advisory Board, and the chair of the Gastrointestinal LACOG (Latin American Cooperative Oncology Group). She is also actively involved in mentoring and teaching of young oncologists.

    Dr Rachel Riechelmann discloses: Advisory board/panel fees from AstraZeneca and Servier (both relationships terminated). Grants/Research Support from Bayer and Libbs.
    Dr Chiara Cremolini

    University of Pisa, Pisa, Italy

    Dr Chiara Cremolini, MD, PhD,  is an associate professor in medical oncology at the University of Pisa in Italy. read more

    Following an MD Degree in 2008, a Master of Science in Clinical Trials, and a Specialty in Medical Oncology at the University of Pisa, she gained her PhD in Clinical Pathophysiology.

    She is mainly committed to the clinical management of patients affected by gastrointestinal malignancies, and is involved in clinical and translational research projects in the field of colorectal oncology. She is responsible for the scientific activities of the Clinical Trials’ Office at the oncology unit at Santa Chiara Hospital in Pisa. She actively contributes to clinical trials run by the Gruppo Oncologico del Nord Ovest (GONO), an Italian foundation involved in the design and execution of clinical and translational studies of several solid malignancies. Dr Cremolini served as the scientific secretary of GONO between 2015 and 2021, and has been the president since 2021. She is a faculty member of European Society for Medical Oncology gastrointestinal tumour group, and has been particularly involved in trials investigating intensified chemotherapy regimens as upfront treatment of metastatic colorectal cancer patients.

    With regard to translational activities, she is mainly interested in the identification of molecular predictors of benefit from systemic treatments, and to this purpose has collaborated with numerous international institutions. She is author of more than 200 papers in the field of colorectal cancer.

    Dr Chiara Cremolini discloses: Advisory board or panel fees from Amgen, Bayer, Merck, Pierre Fabre and Servier. Consultancy fees from Bayer. Grants/Research Support from Bayer, Merck and Servier.
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    touchONCOLOGY touchONCOLOGY
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    Colorectal Cancer, Gastrointestinal Cancers CE/CME accredited

    touchPANEL DISCUSSION
    A visually engaging discussion designed to emulate a ‘live’ panel experience and provide clinicians with practical expert insights to address their clinical challenges. Useful tips below will show how to navigate the activity. Close

    Optimizing strategies for the treatment of colorectal cancer in the biomarker era

    Faculty Podcast Featured
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    • Downloads including slides are available for this activity in the Toolkit
    Learning Objectives

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

    • Choose appropriate first-line treatment for patients with CRC based on biomarker testing and clinical characteristics
    • Compare and contrast the available techniques for biomarker testing recommended for patients with CRC
    • Review the evidence for recent and emerging targeted therapy options for CRC
    Overview

    Dr Kei Muro, Dr Chiara Cremolini and Dr Rachel Riechelmann discuss the role of biomarkers in optimizing the treatment of colorectal cancer, including how they can be used to make first-line treatment decisions, the available and emerging biomarker testing techniques, and how biomarkers are shaping the evolving treatment landscape.

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

    Target Audience

    This activity has been designed to meet the educational needs of oncologists, gastrointestinal oncologists involved in the management of colorectal cancer haematologists (including haemato-oncologists), paediatric haematologists, haematology nurse specialists and nurse practitioners, neonatologists, physician assistants and primary care physicians involved in the management of patients with PK deficiency.

    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 Kei Muro discloses: Advisory board or panel fees from Amgen and AstraZeneca. Consultancy fees from Chugai and Ono. Grants/research support from Amgen, Astellas, Daiichi Sankyo, Eisai, Merck Serono, MSD, Novartis, Ono, Parexel International, Pfizer, Sanofi, Solasia Pharma and Taiho. Speaker’s bureau fees from Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Ono and Taiho.

    Dr Rachel Riechelmann discloses: Advisory board/panel fees from AstraZeneca and Servier (both relationships terminated). Grants/Research Support from Bayer and Libbs.

    Dr Chiara Cremolini discloses: Advisory board or panel fees from Amgen, Bayer, Merck, Pierre Fabre and Servier. Consultancy fees from Bayer. Grants/Research Support from Bayer, Merck and Servier.

    Content reviewer

    Rene D Gomez-Esquivel, MD has no relevant financial relationships to disclose.

    Touch Medical Directors

    Holly Gilbert-Jones 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 1.0 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 1.0 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.

    Date of original release: 19 April 2023. Date credits expire: 19 April 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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    This Activity Is Funded By:

    An independent medical education grant from the Healthcare Business of Merck KGaA, Darmstadt, Germany. This activity is jointly provided by USF Health and touchIME.

    The information provided by this CE 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 CE 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: 19 April 2023. Date credits expire: 19 April 2024.

    Claim Credit
    touchPANEL DISCUSSION
    Optimizing strategies for the treatment of colorectal cancer in the biomarker era
    1.0 CE/CME credit
    Question 1/6
    What is the prevalence of KRAS/NRAS mutations in patients with metastatic CRC?

    CRC, colorectal cancer; KRAS, Kirsten RAS oncogene homolog; NRAS, neuroblastoma RAS oncogene homolog; RAS, rat sarcoma virus.

    The prevalence of the KRAS/NRAS mutations in patients with metastatic CRC is approximately 55%. The BRAF V600E mutation is less common than RAS mutations, affecting only 5–10% of patients with metastatic CRC. It is nearly always mutually exclusive with RAS mutations. Approximately 4% of patients with metastatic CRC have MSI-H/dMMR tumours.

    Abbreviations

    BRAF, v-Raf murine sarcoma viral oncogene homolog B1; CRC, colorectal cancer; dMMR, DNA mismatch repair; KRAS, Kirsten RAS oncogene homolog; MSI-H, microsatellite instability-high; NRAS, neuroblastoma RAS oncogene homolog; RAS, rat sarcoma virus.

    Reference

    Lee MKC, Loree JM. Curr Oncol. 2019;26(Suppl. 1):S7–15.

    Question 2/6
    A patient with metastatic CRC has their level of KRAS and EGFR extracellular domain mutation monitored via ctDNA liquid biopsy. Why would using ctDNA liquid biopsy be particularly helpful?

    CRC, colorectal cancer; ctDNA, circulating tumour DNA; EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma viral oncogene homolog; NTRK, neurotrophic tyrosine receptor kinase.

    Monitoring levels of KRAS and EGFR extracellular domain mutations in ctDNA has shown that tracking kinetics of resistance mutations in blood can be used to guide anti-EGFR rechallenge therapy.1–3

    Abbreviations

    ctDNA, circulating tumour DNA; EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma viral oncogene homolog.

    References

    1. Siravegna G, Bardelli A. Ann Oncol. 2019;30:157–8.
    2. Vera R, et al. Clin Transl Oncol. 2021;23:827–39.
    3. Siravegna G, et al. Ann Oncol. 2019;30:1580–90.
    Question 3/6
    As recommended by the 2022 ESMO and 2022 NCCN guidelines, which of the following patients with metastatic CRC would you test for HER2 amplification?

    BRAF, v-Raf murine sarcoma viral oncogene homolog B1; CRC, colorectal cancer; ESMO, European Society for Medical Oncology; HER2, human epidermal growth factor receptor 2; NCCN, National Comprehensive Cancer Network; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; RAS, rat sarcoma virus.

    The 2022 ESMO clinical practice guidelines for the diagnosis, treatment and follow-up of metastatic CRC state that identification of HER2 amplification is recommended in RAS wild-type patients to detect those who may benefit from HER2 blockade.1 The 2022 NCCN guidelines recommend that HER2 testing is carried out in all patients unless there is a known RAS or BRAF mutation.2

    Abbreviations

    BRAF, v-Raf murine sarcoma viral oncogene homolog B1; CRC, colorectal cancer; ESMO, European Society for Medical Oncology; HER2, human epidermal growth factor receptor 2; NCCN, National Comprehensive Cancer Network; RAS, rat sarcoma virus.

    References

    1. Cervantes A, et al. Ann Oncol. 2023;34:10–32.
    2. NCCN. Colon cancer. 2022. Available at: www.nccn.org/professionals/physician_gls/pdf/colon.pdf  (accessed 14 February 2023).
    Question 4/6
    Your patient with metastatic CRC has previously received folinic acid, fluorouracil and oxaliplatin chemotherapy. Following biomarker testing, your patient has been shown to be carrying a BRAF V600E mutation. According to the 2022 ESMO guidelines, which treatment should you use as a second-line therapy option?

    BRAF, v-Raf murine sarcoma viral oncogene homolog B1; CRC, colorectal cancer; ESMO, European Society for Medical Oncology.

    The BRAF V600E mutation is a strong negative prognostic factor in metastatic CRC. BRAF mutation status should be assessed simultaneously with RAS testing for prognostication. Treatment with cetuximab + encorafenib has shown better response, progression-free survival and overall survival rates than treatment with irinotecan + cetuximab in BRAF V600E-mutant metastatic CRC in second- and third-line treatment. The 2022 ESMO  guidelines state that cetuximab + encorafenib is the recommended therapy option for BRAF V600E pre-treated metastatic CRC.

    Abbreviations

    BRAF, v-Raf murine sarcoma viral oncogene homolog B1; CRC, colorectal cancer; ESMO, European Society for Medical Oncology; RAS, rat sarcoma virus.

    Reference

    Cervantes A, et al. Ann Oncol. 2023;34:10–32.

    Question 5/6
    Prognostic and predictive markers are two classes of biomarkers in oncology. Which of the following statements is true with regard to predictive biomarkers?

    Prognostic markers inform about the likely disease outcomes independent of the treatment received, and predictive markers provide information about the likely outcomes with application of specific interventions. Therefore, predictive markers can help select among two or more therapy options. Predictive markers are of particular importance for targeted therapies, which often are expected to benefit only patients whose disease is characterized by the presence of a biomarker.

    Reference

    Polley MC et al. J Natl Cancer Inst. 2013;20:1677–83.

    Question 6/6
    Your patient has RAS-mutated metastatic CRC that has progressed following fluoropyrimidine, oxaliplatin and irinotecan chemotherapy. According to the 2022 NCCN guidelines, which of the following treatments would you not consider using as a second-line treatment option?

    CRC, colorectal cancer; RAS, rat sarcoma virus.

    Patients with known KRAS or NRAS mutations should not be treated with either cetuximab or panitumumab, either alone or in combination with other anticancer agents, because they have virtually no chance of benefit and the exposure to toxicity and expense cannot be justified.

    Abbreviations

    CRC, colorectal cancer; KRAS, Kirsten RAS oncogene homolog; NRAS, neuroblastoma RAS oncogene homolog; RAS, rat sarcoma virus.

    Reference

    NCCN. Colon cancer. 2022. Available at: www.nccn.org/professionals/physician_gls/pdf/colon.pdf (accessed 14 February 2023).

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    This Activity Is Funded By:

    An independent medical education grant from the Healthcare Business of Merck KGaA, Darmstadt, Germany. This activity is jointly provided by USF Health and touchIME.

    The information provided by this CE 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 CE 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: 19 April 2023. Date credits expire: 19 April 2024.

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