Colorectal cancer, HER2-positive

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search

Back to Top

Section editor
Unfilled
If you are interested in this role, please contact us at [email protected].

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

3 regimens on this page
2 variants on this page


Guidelines

ESMO

Older

Japanese Society for Cancer of the Colon and Rectum

NCCN

SIOG

Advanced or metastatic disease, second or third-line therapy

Pertuzumab & Trastuzumab

Regimen

Study Dates of enrollment Evidence Efficacy
Meric-Bernstam et al. 2019 (MyPathway) 2014-2017 Phase 2a 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 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.

Targeted therapy

  • 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 dosing details in manuscript link to PMC article PubMed Clinical Trial Registry

Lapatinib & Trastuzumab

Regimen

Study Dates of enrollment Evidence Efficacy
Sartore-Bianchi et al. 2016 (HERACLES) 2012-2015 Phase 2 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

Targeted therapy

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 EudraCT 2012-002128-33

Trastuzumab deruxtecan monotherapy

Regimen

Study Dates of enrollment Evidence Efficacy
Siena et al. 2021 (DESTINY-CRC01) 2018-2019 Phase 2 ORR: 45% (95% CI 32-60%)

Biomarker eligibility criteria

  • HER2 amplification

Diagnostic criteria for Her2 positivity in DESTINY-CRC01:

  • Three cohorts were based on the degree of Her2 positivity:
    • HER2-positive with immunohistochemistry (IHC) scoring 3+ or IHC 2+/in situ hybridization (ISH)+ (cohort A, n = 53)
    • HER2 IHC 2+/ISH– (cohort B, n = 7)
    • HER2 IHC 1+ (cohort C, n = 18).

Antibody-drug conjugate therapy

21-day cycles

References

  1. DESTINY-CRC01: Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Komatsu Y, Esaki T, Chung K, Wainberg Z, Sartore-Bianchi A, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T; DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):779-789. Epub 2021 May 4. link to original article contains dosing details in abstract PubMed Clinical Trial Registry

Tucatinib & Trastuzumab

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Awaiting publication (MOUNTAINEER) 2017-NR Phase 2 (RT)

Note: dosing details are from the FDA labeling.

Biomarker eligibility criteria

  • HER2 amplification and KRAS wild-type

Targeted therapy

21-day cycles

References

  1. MOUNTAINEER: Clinical Trial Registry
Retrieved from "https://hemonc.org/w/index.php?title=Colorectal_cancer,_HER2-positive&oldid=72049"