Colorectal Cancer CE/CME ACCREDITED Watch Time: 34 mins

touchEXPERT OPINIONS Optimizing targeted therapy in colorectal cancer: How do the latest data impact clinical practice?

Watch three oncology experts discuss advances in targeted therapies and biomarkers for metastatic colorectal cancer (CRC).

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Prof. Rachel Riechelmann
A.C. Camargo Cancer Center, São Paulo, Brazil
How can we refine first-line therapy choice in mCRC? Molecular biomarkers and clinical features

Prof. Riechelmann discusses guideline-recommended biomarkers and clinical features that help guide first-line treatment choice in mCRC.

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Interview Questions

In this interview, Prof. Riechelmann answers the following questions:

  • What biomarkers and clinical features are available to refine first-line treatment selection in mCRC?
  • What is the role of RAS mutational status when determining first-line treatment for mCRC?
  • Presence of the BRAF-V600E mutation is a known adverse prognostic factor in mCRC: What are the molecular and clinical characteristics of this subgroup of patients?
  • How does knowledge of MSI status help guide treatment choice for patients with mCRC in the first-line setting?
  • How important is location of the primary tumour for first-line mCRC management?
About Prof. Rachel Riechelmann

Prof. Riechelmann is Head of Clinical Oncology at AC Camargo Cancer Center, São Paulo, Brazil. She is a medical oncologist and clinical researcher in the field of gastrointestinal (GI) and neuroendocrine tumours (NETs). read more

Prof. Riechelmann is President of the Brazilian Gastrointestinal Tumour Group (GTG), a scientific committee member of the European Society for Medical Oncology (ESMO; Colorectal and NET) and a member of the Latin American Society of GI Oncology (SLAGO). She is part of the European Society of Neuroendocrine Tumours (ENETS) Scientific Advisory Board and is Chair of the GI Latin American Cooperative Oncology Group (LACOG).

Prof. Riechelmann has published more than 100 articles in peer-reviewed journals and has authored a book titled, ‘Methods and Biostatistics in Oncology: Understanding Clinical Research as an Applied Tool’ (Springer, 2018).

Prof. Rachel Riechelmann discloses: Consulting fees from AstraZeneca, Bayer, Merck, MSD, Roche and Servier; Speakers bureau fees from Bayer, Roche and Servier; Research support from Amgen and Bayer.

 
Dr Diana Hanna
Hoag Cancer Center and Keck School of Medicine of University of Southern California, California, USA
How to address resistance to anti-EGFR therapy: A focus on rechallenge therapies

Dr Hanna outlines the rationale and evidence for anti-EGFR rechallenge strategies in mCRC and the potential role of liquid biopsy in this setting.

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Interview Questions

In this interview, Dr Hanna answers the following questions:

  • Why is rechallenge with anti-EGFR treatments an important strategy in mCRC?
  • What mechanisms are involved in resistance to anti-EGFR therapies?
  • What is the evidence for rechallenge with anti-EGFR therapies in RAS wt mCRC?
  • What ongoing trials are investigating different rechallenge strategies for RAS wt mCRC?
  • What is the role of liquid biopsy ctDNA testing in guiding rechallenge therapy in mCRC?
About Dr Diana Hanna

Dr Hanna is an oncology specialist practising at the Hoag Cancer Center and Keck School of Medicine, University of Southern California (USC), USA. read more

Dr Hanna earned her medical degree from the University of California, Davis, and is board-certified in internal medicine and medical oncology. She completed her Hematology/Oncology Fellowship at USC, where she served as Chief Fellow.

Dr Hanna’s research interests include investigation of predictive and prognostic biomarkers in gastrointestinal malignancies and clinical trial protocol development.

Dr Diana Hanna has no financial interests/relationships or affiliations to disclose in relation to this activity.

 
Prof. Takayuki Yoshino
National Cancer Center Hospital East, Kashiwa, Japan
Treatment of BRAF-V600E-mutated mCRC: Current landscape and latest data

Prof. Yoshino discusses the challenges of treating patients with BRAF-V600E-mutated mCRC and reviews the latest clinical trial data for emerging therapies in this field.

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Interview Questions

In this interview, Prof. Yoshino answers the following questions:

  • What are the challenges in the treatment of patients with BRAF-mutated mCRC?
  • What is the current treatment approach for patients with BRAF-V600E-mutated mCRC?
  • What are the latest data from the BEACON trial, which aims to investigate the use of BRAF, MEK, and EGFR inhibitors in BRAF-V600E-mutated mCRC in the second-line setting?
  • What data are available for a combination approach using BRAF, MEK and EGFR inhibitors in BRAF-V600E-mutated mCRC in the first-line setting?
  • What other potential targets are being explored for the treatment of BRAF-V600E-mutated mCRC?
About Prof. Takayuki Yoshino

Prof. Yoshino is Director of the Department of Gastroenterology and Gastrointestinal Oncology, and the Head of the Clinical Research Coordinating Division at the National Cancer Center Hospital East (NCCE) in Kashiwa, Japan. He has a particular interest in chemotherapies for gastrointestinal cancers, especially CRC, and focuses on new, investigational agents and translational research. read more

Prof. Yoshino has published more than 200 articles in peer-review journals on the topic of metastatic CRC (mCRC), with several articles published in the Lancet, Journal of Clinical Oncology, The New England Journal of Medicine and Nature Medicine.

In addition, he holds several professional appointments, serving as an International Guideline Member for the European Society of Medical Oncology (ESMO), Chair of the Pan-Asian adapted ESMO Guideline for mCRC and an American Society of Clinical Oncology (ASCO) advisory committee member. Prof. Yoshino is also part of the administrative board and is Vice Chair of the Japanese Society of Medical Oncology (JSMO) and the Japan Society of Clinical Oncology (JSCO) international affairs committees.

Prof. Takayuki Yoshino discloses: Research support from Amgen, Chugai Pharmaceutical, Daiichi Sankayo, MSD, Ono Pharmaceutical, Parexel International, Sanofi, Sumitomo Dainippon Pharma and Taiho Pharmaceutical Co. Ltd.

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Overview & Learning Objectives
Overview

In this activity, three leading experts discuss the role of biomarkers in selecting first-line treatment for metastatic CRC, rechallenge strategies with anti-epidermal growth factor receptor (EGFR) therapies and the latest clinical data for BRAF-V600E-mutated tumours.

This activity has been jointly provided by Oakstone and touchIME for touchONCOLOGY. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians. read more

Target Audience

This activity has been designed to meet the educational needs of oncologists, including gastrointestinal specialists involved in the management of colorectal cancer, based globally.

Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest have been mitigated. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relationships with ineligible entities.

Faculty

Prof. Rachel Riechelmann discloses: Consulting fees from AstraZeneca, Bayer, Merck, MSD, Roche and Servier; Speakers bureau fees from Bayer, Roche and Servier; Research support from Amgen and Bayer.

Dr Diana Hanna has no financial interests/relationships or affiliations to disclose in relation to this activity.

Prof. Takayuki Yoshino discloses: Research support from Amgen, Chugai Pharmaceutical, Daiichi Sankayo, MSD, Ono Pharmaceutical, Parexel International, Sanofi, Sumitomo Dainippon Pharma and Taiho Pharmaceutical Co. Ltd.

Content Reviewer

Walter Murray Yarbrough, MD, FACP has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Hennah Patel, MPharm, RPh, has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

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 the joint providership of Oakstone Publishing and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education for physicians.

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 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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

Date of original release: 06 May 2021. Date credits expire: 06 May 2022.

Learning Objectives

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

  • Identify appropriate first-line therapies for patients with colorectal cancer according to the primary tumour site and molecular profile
  • Discuss the rationale for rechallenge using anti-EGFR therapies and the potential treatment benefits for patients with CRC
  • Analyse the most recent data for therapy for patients with BRAF-mutation-positive colorectal cancer
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Question 1/5
Your patient receives a primary diagnosis of mCRC. How will you determine first-line systemic treatment?

BRAF, v-Raf murine sarcoma viral oncogene homolog B; CMS, consensus molecular sub-type; mCRC, metastatic colorectal cancer; MSI, microsatellite instability; RAS, rat sarcoma oncogene; TMB, tumour mutational burden.
Correct

Targeted treatment regimens have become an important part of the mCRC treatment landscape. The most recent (as of March 2021) ESMO/ESMOASIA and NCCN guidelines recommend biomarker testing to determine gene tumour status for KRAS/NRAS and BRAF mutations as well as MSI/MMR status in patients with mCRC, to identify actionable genetic alterations.1–3 NCCN guidelines also recommend testing for HER2 and NTRK fusions in RAS and BRAF wt tumours.3

BRAF, v-Raf murine sarcoma viral oncogene homolog B; CMS, consensus molecular sub-type; ESMO, European Society for Medical Oncology; HER2, human epidermal growth factor receptor 2; KRAS, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; mCRC, metastatic colorectal cancer; MMR, mismatch repair; MSI, microsatellite instability; NCCN, National Comprehensive Cancer Network; NRAS, neuroblastoma RAS oncogene homolog; NTRK, neurotrophic tyrosine receptor kinase gene; RAS, rat sarcoma oncogene.

References
1. Van Cutsem E, et al. Ann Oncol. 2016;27:1386–422.
2. Yoshino T, et al. Ann Oncol. 2018;29:44–70.
3. NCCN Clinical Practice Guidelines – Colon Cancer v.2.2021. Updated January 21, 2021. Available at: www.nccn.org/professionals/physician_gls/pdf/colon.pdf (accessed 29 March 2021).

Question 2/5
Your patient has been diagnosed with mCRC and is found to have a left-sided RAS wt MSS primary tumour. Based on current guideline recommendations, what would you preferably select as first-line treatment for this patient?

mCRC, metastatic colorectal cancer; MSS, microsatellite stability; RAS, rat sarcoma oncogene; wt, wild-type.
Correct

ESMO/ESMOASIA and NCCN guidelines recommend treatment for newly diagnosed patients with left-sided RAS wt mCRC is with anti-EGFR agents (cetuximab or panitumumab) plus chemotherapy.1–3

EGFR, epidermal growth factor receptor; ESMO, European Society for Medical Oncology; mCRC, metastatic colorectal cancer; NCCN, National Comprehensive Cancer Network; RAS, rat sarcoma oncogene; wt, wild-type.

References
1. Van Cutsem E, et al. Ann Oncol. 2016;27:1386–422.
2. Yoshino T, et al. Ann Oncol. 2018;29:44–70.
3. NCCN Clinical Practice Guidelines – Colon Cancer v.2.2021. Updated January 21, 2021. Available at: www.nccn.org/professionals/physician_gls/pdf/colon.pdf (accessed 29 March 2021).

Question 3/5
Which of the following statements best reflects current evidence for anti-EGFR rechallenge therapy in patients with mCRC?

EGFR, epidermal growth factor receptor; mCRC, metastatic colorectal cancer; RAS, rat sarcoma oncogene; wt, wild-type.
Correct

Several studies have demonstrated the benefit of anti-EGFR rechallenge therapy in specific mCRC patient groups who previously responded to anti-EGFR treatment but later experienced disease progression.1–4 One study found that patients with RAS wt mCRC may be more likely to benefit from rechallenge therapy versus patients with RAS-mutated mCRC.1

EGFR, epidermal growth factor receptor; mCRC, metastatic colorectal cancer; RAS, rat sarcoma oncogene; wt, wild-type.

References
1. Santini D, et al. Ann Oncol. 2012;23:2313e2318.
2. Cremolini C, et al. JAMA Oncol. 2019;5:343e350.
3. Karani A, et al. Ecancermedicalscience. 2020;14:1069.
4. Chong L, et al. Target Oncol. 2020;15:751–7.

Question 4/5
Your patient with BRAF-V600E-mutated mCRC has had a poor response to standard first-line chemotherapy. Based on 2021 NCCN guidelines, what is the recommended treatment approach for this patient?

BRAF, v-raf murine sarcoma viral oncogene homolog B; EGFR, epidermal growth factor receptor; mCRC, metastatic colorectal cancer; NCCN, National Comprehensive Cancer Network.
Correct

The 2021 NCCN guidelines recommend using the FDA-approved approach of encorafenib plus cetuximab or panitumumab for previously treated BRAF-V600E-mutated mCRC.1,2

BRAF, v-raf murine sarcoma viral oncogene homolog B; EGFR, epidermal growth factor receptor; FDA, US Food and Drug Administration; mCRC, metastatic colorectal cancer; NCCN, National Comprehensive Cancer Network.

References
1. FDA. FDA approves encorafenib in combination with cetuximab for metastatic colorectal cancer with a BRAF-V600E mutation. April 2020. Available at: www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-encorafenib-combination-cetuximab-metastatic-colorectal-cancer-braf-v600e-mutation#:~:text=On%20April%208%2C%202020%2C%20the,approved%20test%2C%20after%20prior%20therapy (accessed 29 March 2021).
2. NCCN Clinical Practice Guidelines – Colon Cancer v.2.2021. Updated January 21, 2021. Available at: www.nccn.org/professionals/physician_gls/pdf/colon.pdf (accessed 29 March 2021).

Question 5/5
What were the main efficacy outcomes of the phase III BEACON study, in which treatment with encorafenib + cetuximab ± binimetinib was compared with standard chemotherapy plus cetuximab (control) in previously treated BRAF-V600E-mutated mCRC?

BRAF, v-raf murine sarcoma viral oncogene homolog B; mCRC, metastatic colorectal cancer; PFS, progression-free survival; ORR overall response rate; OS, overall survival.
Correct

Data from the phase III BEACON trial led to the approval of doublet therapy comprising encorafenib + cetuximab, in BRAF-V600E-mutated mCRC following previous therapy.1–3

In the BEACON trial, encorafenib + cetuximab ± binimetinib improved OS, ORR and PFS in previously treated patients with BRAF-V600E-mutated mCRC versus standard chemotherapy + cetuximab (control).1–3 In addition, doublet or triplet therapy was associated with a substantial improvement of patient-reported QOL versus control.4

BRAF, v-raf murine sarcoma viral oncogene homolog B; mCRC, metastatic colorectal cancer; PFS, progression-free survival; QOL, quality of life; ORR overall response rate; OS, overall survival.

References
1. NCT02928224. Available at: clinicaltrials.gov (accessed 29 March 2021).
2. Kopetz S, et al. J Clin Oncol. 2020;38:Abstr 4001.
3. Tabernero J, et al. J Clin Oncol. 2021;39:273–84.
4. Kopetz S, et al. J Clin Oncol. 2020;38:Abstr 8.

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