Armando Orlandi, Medical Director at the Agostino Gemelli University Hospital Foundation IRCCS, shared a post on LinkedIn:
“ASCO26 | Metastatic Breast Cancer Oral Session — Key Takeaways
The recurring question: when 1L data are positive, does benefit carry downstream? Several PFS2 analyses said yes — plus new players and one instructive miss
TNBC: ADCs deepen, a bispecific arrives
- ASCENT-04 PFS2 (LBA1000): SG + pembro held beyond progression (PFS2 HR 0.67; 24-mo 64% vs 46%) despite 81% crossover.
- ASCENT-03 PFS2 (#1001): in IO-ineligible mTNBC, SG kept its edge (18.2 vs 14.0 mo; HR 0.70).
- TROPION-Breast02 (#1002): 1L Dato-DXd showed consistent downstream gains (PFS2 HR 0.61; TFST HR 0.49).
- Iza-bren (LBA1003): first-in-class EGFR×HER3 bispecific ADC in pretreated TNBC — PFS 8.5 vs 3.1 mo (HR 0.29), OS HR 0.60, but heavy myelosuppression.
HER2-positive
- HER2CLIMB-05 (#1005): tucatinib added to trastuzumab/pertuzumab maintenance improved PFS across every subgroup (24.9 vs 16.3 mo; HR 0.64), brain mets included.
HR+/HER2−: SERDs, ctDNA, PAM pathway
- persevERA (LBA1006): 1L giredestrant + palbociclib did not meet its primary endpoint vs letrozole + palbociclib (HR 0.89; p=0.155) — +4.9 mo numerically; An oral SERD short of the CDK4/6i bar.
- SERENA-6 PFS2 (LBA1007): ctDNA-guided switch to camizestrant at ESR1m emergence sustained benefit (PFS2 HR 0.63; 30-mo PFS 30% vs 3%) regardless of PIK3CA/TP53 — OS still immature.
- VIKTORIA-1 (LBA1008): gedatolisib + fulvestrant ± palbociclib beat alpelisib/fulv in PIK3CA-mutant disease (triplet HR 0.50), with far less hyperglycemia — perhaps the most complete PI3K/AKT/mTOR (PAM) inhibitor for 2L, though more stomatitis.
Supportive care
SAKK REDUSE (#1004): denosumab every 12 weeks was non-inferior to every 4 weeks for skeletal events (HR 1.02), with less hypocalcemia/ONJ — less burden and cost.
Methods corner: credit to ASCENT-03/04 and especially TROPION-Breast02 for handling exploratory PFS2/TFST/TSST correctly — HRs with CIs and, in TROPION-Breast02, rightly no p-value at all (not even nominal). That’s how exploratory endpoints should read: let the estimate speak, no significance theatre.
Bottom line: in TNBC the ADC benefit is durable beyond progression, with a bispecific entering the field; HER2+ maintenance broadens; in HR+ disease, ctDNA-guided switching and pan-PAM inhibition advance while 1L oral SERD combos still struggle vs the CDK4/6i standard. And the one change you can apply tomorrow morning: denosumab Q12W — same protection, less burden, less cost.”
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