Armando Orlandi, Medical Director at the Agostino Gemelli University Hospital Foundation IRCCS, shared a post on LinkedIn:
“ASCO26 | Metastatic Breast Cancer Rapid Oral Session — Key Takeaways
The advanced-disease session was about refining sequence and selection: ADCs maturing, oral SERDs extending their reach, and a few honest reminders of where we still fall short
ADCs consolidating in advanced TNBC
- ASCENT-04 (#1013): in 1L PD-L1+ mTNBC, sacituzumab govitecan + pembrolizumab improved PFS across all Trop-2, tBRCA and HER2 subgroups, largest at high Trop-2 (Q3–Q4 HR ~0.46–0.57).
- ASCENT-03 (#1014): in 1L TNBC not eligible for IO, SG beat chemo consistently (tBRCA WT HR 0.70; HER2 IHC0 HR 0.63) — a frontline option independent of Trop-2 level.
- FUTURE 2.0 (#1020): in basal-like immune-suppressed TNBC, adding bevacizumab to an ADC raised ORR (40% → ~84–87%) and PFS (9.2 vs 4.6 mo; HR 0.47). Intriguing synergy — but phase II, pending confirmation.
Endocrine sequencing after CDK4/6i
- evERA BC (#1016): giredestrant + everolimus sustained benefit beyond first progression (PFS2 HR 0.69; chemo-free survival HR 0.61), regardless of ESR1 status — supporting strategies that delay chemotherapy.
- PATHWAY final OS (LBA1018): palbociclib + tamoxifen ± goserelin confirmed strong PFS (24.4 vs 11.1 mo; HR 0.59), yet OS again missed significance (HR 0.77; p=0.093). The PFS–OS disconnect across the CDK4/6i field persists.
- AMBITION (#1019): adding atezolizumab to paclitaxel + bevacizumab did not improve PFS (HR 0.88; p=0.17) — luminal disease stays immunologically “cold.”
Real-world evidence
PALMARES-2 (#1017, TOP Prof Claudio Vernieri): the first large real-world analysis of continuing 1L ET+CDK4/6i beyond progression in HR+/HER2−. In selected (often oligoprogressive) patients, continuation tracked with longer rwOS (71.3 vs 44.7 mo). Selection bias contributes, but it’s a meaningful first signal in a previously evidence-free setting.
HER2-positive
DESTINY-Breast09 (#1021): depth of response to 1L T-DXd + pertuzumab tracked with durability (24-mo PFS 85% in CR vs 36% in SD/PD). ILD ~12% across groups — ongoing vigilance needed.
A wider lens
Food access & poverty (#1015): in MBC, food-desert residence was linked to distinct ctDNA profiles (more RTK/RAS, CCNE1) and shorter survival — most starkly in Black patients in low-access areas (OS 11 vs 38 mo). A case for integrating social determinants into how we read tumor biology.
Bottom line: ADCs are becoming the TNBC backbone, oral SERD combinations are reshaping post-CDK4/6i sequencing, IO remains ineffective in luminal disease — and the PFS–OS gap, alongside where patients live, keeps us honest.”
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