Colorectal cancer, HER2-positive

Page editor		Section editor
	Ryan Nguyen, DO University of Illinois at Chicago Chicago, IL LinkedIn		Neeta K. Venepalli, MD, MBA University of Illinois at Chicago Chicago, IL

Note: the page has regimens specific to Her2-amplified colon cancer.

• See the main colon cancer page for general regimens.

3 regimens on this page 2 variants on this page

Guidelines

ESMO

• 2016: Van Cutsem et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. PubMed

Older

• 2013: Labianca et al. Early Colon Cancer: ESMO Clinical Practice Guidelines PubMed
• 2013: Balmaña et al. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. PubMed

Japanese Society for Cancer of the Colon and Rectum

• 2016: Watanabe et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer PubMed

NCCN

• NCCN Guidelines - Colon Cancer

SIOG

• 2014: Papamichael et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013

Advanced or metastatic disease, second or third-line therapy

Pertuzumab & Trastuzumab

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Regimen

Study	Evidence	Efficacy
Meric-Bernstam et al. 2019 (MyPathway)	Phase II	ORR: 32% (95% CI 20-45%)

Biomarker eligibility criteria

HER2 amplification

Patients enrolled in MyPathway had ECOG 0-2

Diagnostic criteria for Her2 positivity in MyPathway:

• Patients with solid tumors that have HER2 overexpression, amplification, or HER2-activating mutation as identified by assays performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
  • Assays using in situ hybridization (fluorescence in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]) must indicate the presence of gene amplification with a HER2/CEP17 ratio of ≥ 2.0 or HER2 gene copy number > 6.0.
  • Assays using IHC must indicate a score of 3 +.
  • Assays using next generation sequencing (NGS) of genes with known or potentially clinically relevant alterations or analysis by real-time polymerase chain reaction (RT-PCR) must identify clinically activating mutations (those with major coding disruptions resulting in an amino acid change that is likely to be detrimental to protein function, including premature stop codons or frameshift mutations early in the coding region) or copy number gain.
  • In cases where multiple assays are done, HER2 positivity by any of the testing methodologies would make the patient eligible as long as eligibility criteria are fulfilled.

Chemotherapy

• Pertuzumab (Perjeta) as follows:
  • Cycle 1: 840 mg IV once on day 1
  • Cycle 2 onwards: 420 mg IV once on day 1
• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

1. MyPathway: Meric-Bernstam F, Hurwitz H, Raghav KPS, MCwilliams RR, Fakih M, VanderWalde A, Swanton C, Kurzrock R, Burris H, Sweeney C, Bose R, Spigel DR, Beattie MS, Blotner S, Stone A, Schulze K, Cuchelkar V, Hainsworth J. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019 Apr;20(4):518-530. Epub 2019 Mar 8. link to original article contains verified protocol PubMed

Lapatinib & Trastuzumab

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Regimen

Study	Evidence	Efficacy
Sartore-Bianchi et al. 2016 (HERACLES)	Phase II	ORR: 30% (95% CI 14-50%)

Biomarker eligibility criteria

KRAS wild-type, HER2 amplification

Patients enrolled in HERACLES had ECOG 0-1

Diagnostic criteria for Her2 positivity in HERACLES:

• Tumours with 3+ HER2 score in more than 50% of cells by immunohistochemistry

or

• 2+ HER2 score and a HER2:CEP17 ratio higher than two in more than 50% of cells by FISH

Chemotherapy

• Lapatinib (Tykerb) 1000 mg PO once per day
• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 4 mg/kg IV once on day 1
  • Cycle 2 onwards: 2 mg/kg IV once on day 1

7-day cycles

References

1. HERACLES: Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 Jun;17(6):738-746. Epub 2016 Apr 20. link to original article PubMed