Armando Orlandi, Medical Director at the Agostino Gemelli University Hospital Foundation IRCCS, shared a post on LinkedIn:
“ASCO 2026 — Breast Cancer: The 5 answers that could change clinical practice (and the new questions they open!)
A few days ago I shared 5 questions. Chicago has answered them — what changes, what doesn’t, and what we carry home.
- SENOMAC — YES. Omitting completion axillary dissection for 1–2 SLN macrometastases is safe: 5-yr OS 94.4% vs 93.4% (HR 0.84), BCSS non-inferior, less arm morbidity. Z0011 effectively extended to the macromet setting — de-escalation becomes the default for a vast population.
- OPTIMA — YES (with a caveat) A ROR-directed strategy was non-inferior (5-yr IBCFS 90.4% vs 91.5%; HR 0.99), letting 68% of high-risk ER+/HER2− patients skip chemo — including premenopausal women on OFS and N2 disease. The caveat: in a late-relapsing disease, longer follow-up is essential. With ADAPT/PlanB (no edge of neoadjuvant vs adjuvant chemo), the message converges: operate first, let genomics guide adjuvant therapy.
- SAKK REDUSE — YES, immediately practice-changing. Denosumab every 12 weeks was non-inferior to every 4 weeks (HR 1.02), with less hypocalcemia and ONJ. Same protection, fewer visits, lower cost — applicable tomorrow, for every patient with bone metastases.
- Izalontamab brengitecan — YES. The first-in-class EGFR×HER3 bispecific ADC beat physician’s choice chemo in pretreated TNBC on both endpoints (PFS HR 0.29; OS HR 0.60). A genuinely new class — tempered by substantial myelosuppression.
- persevERA to SERENA-6 — the oral SERD story, rewritten persevERA was negative: giredestrant and palbociclib did not beat letrozole and palbociclib in 1L (HR 0.89). The AI keeps its crown. But SERENA-6 answered the better question — for whom, and when: a ctDNA-guided switch to camizestrant at ESR1m emergence improved PFS2 (HR 0.63; 30-mo PFS 30% vs 3%). OS still immature — but ctDNA monitoring’s door is now open.
Negative and instructive trials
- AMBITION: atezolizumab failed in HR+/HER2− — luminal stays immunologically cold.
- PATHWAY: palbociclib and tamoxifen gained PFS but missed OS — the Palbociclib PFS–OS gap persists.
- AXSANA: axillary response to NACT is driven by biology, not nodal burden.
Three new questions
- Neoadjuvant chemo offers no edge in luminal disease, and ‘surgery first’ now looks like ‘the rule’. Could chemo-immunotherapy, or next-gen endocrine therapy and targeted agents, rewrite that rule and bring neoadjuvant back on new grounds?
- ADC sequencing was already complex — now, with SG, Dato-DXd, T-DXd and a HER3 bispecific crowding the same patients, ever more tangled, with no prospective data. How do we sequence ADC after ADC, and is there cross-resistance by payload or target?
- ctDNA monitoring: SERENA-6 validates the concept — but is operationalizing serial ctDNA, and proving it improves OS (not just PFS2), the next frontier?
Chicago delivered. The answers reshape practice today, the questions will define the trials of tomorrow.”
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