HER2-positive breast cancer: guideline history

Anchored to: FDA approvals of pertuzumab (June 2012, CLEOPATRA) and trastuzumab emtansine (February 2013, EMILIA)

• addedMetastatic, first line: Docetaxel, trastuzumab and pertuzumab as the preferred first-line regimen.
• addedMetastatic, second line: Trastuzumab emtansine as the preferred second-line agent.

Anchored to: FDA approval of adjuvant trastuzumab emtansine for residual disease, May 2019 (KATHERINE)

• addedPost-neoadjuvant, residual invasive disease: Trastuzumab emtansine for 14 cycles replaces trastuzumab when invasive disease remains after neoadjuvant therapy.

Anchored to: FDA approval of tucatinib, April 2020 (HER2CLIMB)

• addedMetastatic, later lines and brain metastases: Tucatinib with trastuzumab and capecitabine after one or more HER2 regimens, including patients with brain metastases.

Anchored to: FDA approval of trastuzumab deruxtecan in the second line, May 2022 (DESTINY-Breast03)

• recategorisedMetastatic, second line: Trastuzumab deruxtecan becomes the preferred second-line regimen; trastuzumab emtansine moves to later lines.T-DM1 preferred → T-DXd preferred (category 1); T-DM1 other recommended

Anchored to: FDA approval of trastuzumab deruxtecan with pertuzumab in the first line, 2025 (DESTINY-Breast09)

• addedMetastatic, first line: Trastuzumab deruxtecan plus pertuzumab listed as a preferred first-line option alongside taxane, trastuzumab and pertuzumab.

Anchored to: Approval of trastuzumab deruxtecan for residual disease after neoadjuvant therapy, 2026 (DESTINY-Breast05)

• recategorisedPost-neoadjuvant, residual invasive disease: Trastuzumab deruxtecan supersedes trastuzumab emtansine for residual invasive disease after neoadjuvant therapy.T-DM1 (KATHERINE) → T-DXd (DESTINY-Breast05, iDFS HR 0.47)