Armando Orlandi, Medical Director at the Agostino Gemelli University Hospital Foundation IRCCS, shared on LinkedIn:
“ESMO 2026 Madrid: beyond the 5 Questions and 5 Answers!
Findings I did not expect, and keep thinking about
Intrathecal anti-HER2 is back!
INSPIRE-LM (1768RO), phase II: 30 patients with HER2+ leptomeningeal metastases (LM), radiotherapy followed by intrathecal trastuzumab + pertuzumab
- Median overall survival (OS) 36.2 months, 12-month OS 79%
- LM progression-free survival (PFS) 19.3 months
- 17% complete LM responses, mostly mild toxicity, one patient still on treatment at 38.7 months
In a setting where survival was historically counted in months, these numbers are unprecedented
Small, selected cohort; ongoing systemic therapy allowed.
- Read it alongside BRIDGET (1767RO): tucatinib added after radiosurgery for isolated brain progression, 59% intracranial PFS at 18 months.
- An old route of administration, re-read with new drugs.
HER2-low: the antibody-drug conjugates (ADCs) from China
Two phase III trials vs chemotherapy:
- HORIZON-Breast06 (LBA13): trastuzumab rezetecan, PFS 16.4 vs 6.8 months, hazard ratio (HR) 0.27; interstitial lung disease (ILD) 2.5%
- APEX-Breast01 (LBA27): TQB2102 in HR+/HER2-low after CDK4/6 inhibitors, PFS 16.4 vs 5.5 months, HR 0.29; ILD 2.2%
For reference, DESTINY-Breast06 (trastuzumab deruxtecan): 13.2 vs 8.1 months, HR 0.62.
Before getting excited:
Control arms at 5.5–6.8 months vs 8.1 in DB-06: a weaker comparator inflates the HR
Grade ≥3 toxicity 84% vs 68% with trastuzumab rezetecan
OS immature; access outside China undefined
And after SWITCH (4RO): if the topoisomerase-I payload moves earlier, what comes next?
Omitting radiotherapy AND endocrine therapy: the bill arrivesTOP-1 (545RO): 792 women aged ≥70, low-risk ER+ disease, breast-conserving surgery alone
- 5-year local recurrence 14.8%, above the 10% the study was designed to exclude
- Breast cancer deaths: 2 of 792
LUMINA and PRIME II dropped radiotherapy but kept endocrine therapy. Dropping both is a different story.
Still an option, but only through honest shared decision-making: excellent survival, yet about 1 in 7 women faces a local recurrence.
Also worth a look.
GIM3-FATA (544RO): Italian trial, exemestane worse than anastrozole for disease-free survival (HR 1.23)
PREDICTHER (LBA17): negative HER2-PET predicted non-response to trastuzumab deruxtecan in 10/10 HER2-low/0 patients
AIUR (LBA28): Surgical gloves against paclitaxel neuropathy. Primary endpoint missed, but grade ≥2 neuropathy 59% vs 82%
What struck you most in Madrid?”
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