Breast: Metastatic HER2-positive and CDK4/6

Why D is correct

CLEOPATRA established first-line dual HER2 blockade with pertuzumab plus trastuzumab and docetaxel as standard for HER2-positive metastatic breast cancer, with median overall survival of 57.1 months versus 40.8 months for trastuzumab and docetaxel alone (HR 0.69). Despite co-existing ER positivity, HER2-positive metastatic disease is treated first-line with the CLEOPATRA regimen.

And why the others are not

• AIncorrect. Capecitabine plus lapatinib is a later-line HER2-directed option, not the first-line standard established by CLEOPATRA.
• BIncorrect. Omitting pertuzumab forgoes the proven overall survival benefit of dual HER2 blockade demonstrated in CLEOPATRA.
• CIncorrect. T-DM1 is a second-line HER2-directed therapy, not first-line in this setting.
• EIncorrect. Endocrine therapy with a CDK4/6 inhibitor is first-line for HR-positive, HER2-negative disease; it does not address the HER2-positive driver here.

Source CLEOPATRA - first-line dual HER2 blockade in metastatic breast cancer (end-of-study) — Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519-530.