touchPANEL DISCUSSION

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

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

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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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Topics covered in this activity

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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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