Intel @IntelMedicine

PD(L)1-VEGF bispecifics are already beating PD1 inhibition alone in trials, so what's next? This trial (BioNTech, DualityBio, BMS) adds a new B7-H3 ADC to a PDL1-VEGF bispecific, with potential synergy: 1) VEGF blockade: normalizes tumor vasculature, improves ADC delivery and T cell infiltration. 2) B7-H3 ADC: kills cancer cells, triggers immunogenic inflammation. 3) PDL1 blockade: releases immune suppression, allows T cells to exploit immune response induced by ADC. Confirmed ORR up to 71% -- in immune-cold platinum-resistant ovarian cancer. The broader, ongoing phase 2 includes colorectal cancer, pancreatic cancer and other tumor types.

.@nlinmd, joins as an invited discussant for two studies exploring treatment approaches for CNS tumors: final results from the phase 2 TUXEDO-3 trial of patritumab deruxtecan in active brain metastases and leptomeningeal disease, and a first-in-human phase 1 study of intrathecal peptide-pulsed dendritic cells for leptomeningeal disease in patients with HER2-positive and triple-negative breast cancer. #ESMO26

#ESMO26 Starting Adjuvant CDK4/6i? Let’s Revisit the TRADE Study on Abemaciclib Dose Escalation.

Some tentative good news today for a vaccine in pancreas cancer. - 7-valent mutant KRAS vaccine (G12D, G12R, G12V, G12A, G12C, G12S and G13D) given after surgery and completion of chemotherapy (with or without radiotherapy) in patients with stage I-III KRAS-mutant pancreas cancer. - This did not prevent recurrence in the overall population. - But, when split into pre-specified groups: ctDNA+ vs. ctDNA-, or presence/absence of prior radiation, there was significant (and substantial) protection. - It's unclear how this KRAS vaccine will interact with KRAS inhibitors in the future. The vaccine is made by Elicio Therapeutics, the data were presented by Eileen O'Reilly at ESMO - it's now moving to phase 3.

#ESMO26 | HORIZON-Breast06 Impressive PFS benefit✨️ In HER2-low mBC, trastuzumab rezetecan significantly improved PFS vs chemo: 16.4 vs 6.8 mo Benefit was consistent in HR+ (HR 0.24) and HR− (0.34) pts OS remains immature, but an encouraging trend is emerging (HR 0.67).

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Yakup Ergün @dr_yakupergun

3 days ago

#ESMO26 | HORIZON-Breast06 HER2-low mBC after ≥1 prior line of chemo for metastatic disease, or in the first-line chemo setting after prior ET (if HR+). Trastuzumab rezetecan vs. physician’s choice of chemo PFS: 16.4 vs 6.8 mo (HR 0.27) ORR: 75.5% vs 41.2% Grade ≥3 TRAEs:

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#ESMO26 | NSABP B-42 – 15-year final analysis After 5 years of AI-based therapy, an additional 5 years of letrozole: • DFS: 61.6% vs 56.5% (HR 0.85). • Distant recurrence: 6.9% vs 9.7% (HR 0.72). The sustained reduction in distant recurrence is valuable. Given changes in post-recurrence treatment over such a long follow-up, I do not consider OS alone decisive. However, SALSA did not demonstrate superiority of 10 over 7 years, nor did IDEAL demonstrate superiority of 10 over 7.5 years. B-42 compares 5 with 10 years. Several questions remain: • In which patients is 10 years superior to 7–8 years? • Should we go beyond 10 years? • When adjuvant CDK4/6 inhibitors are added, should we still extend endocrine therapy for this long? Personally, I favour extending treatment to 10 years, particularly in patients at high risk of late recurrence who tolerate therapy well, and perhaps longer in selected patients.

As part of JCI’s review series on therapeutic strategies in #BreastCancer, Antonio Giordano @antgiorda & colleagues @danafarber present: Next-generation CDK inhibitors in hormone receptor-positive/ HER2-negative breast cancer: doi.org/10.1172/JCI207… Inhibitors of cyclin-dependent kinases (CKDs) are an important component of treatment for both early stage and metastatic breast cancer. However, these agents can cause hematologic toxicity, and many patients eventually develop resistance. In this Review, the authors describe the development of novel CDK-targeted therapies that are enabling more precise and durable therapy.

HR+/HER2-の薬剤開発状況、AKTiやCDK4i、HR+HER2-MBCへのペムブロに関するDisucussion。 乳がんは、CDK6よりもCDK4依存が強い。 HR+ではPD-L1がそもそもに頻度低く、これ以上の対象を絞っていくのは難しそう。でも、一部にduration responseはいる。この対象の免疫療法は開発課題は色々ありそうだ。 #ESMO26

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Presented at #ESMO26: In a prespecified interim analysis of a phase 3 trial involving patients with extensive-stage SCLC, the median overall survival was 21.1 months with tarlatamab–durvalumab maintenance therapy and 12.7 months with durvalumab alone. Full DeLLphi-305 trial results: nej.md/4iveIgW @myESMO

#BSTRONGER 🤯 that 95.1% of pts w/ stage I-III TNBC had ctDNA at baseline!!! Wow. By C3, >80% pts had cleared ctDNA in response to chemo Molecular response was associated with tumor burden: 100% stage I 85% stage II 44% stage III, cleared #ESMO26 #ESMOAmbassadors @OncoAlert

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Helpful summary table on ADC-related eye toxicity #ESMO26 More stable linkers associated with greater toxicity. Befriend an opthalmologist and have them be part of your toxicity dream team! 👁️

#ESMO26 | evERA – Biomarker Analysis In the post-CDK4/6 setting, the PFS benefit of giredestrant + everolimus was maintained in patients with single and multiple ESR1 mutations (HR 0.38 and 0.48), and across clonal and subclonal variants. High ctDNA tumour fraction was associated with poorer prognosis, but benefit remained evident: PFS 7.4 vs 4.6 months; HR 0.52. Encouraging results despite biological heterogeneity. However, uncertainty in small subgroups means these exploratory findings are not yet sufficient to guide variant-specific treatment selection.

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A crucial discussion point at #ESMO26: the control arm matters! In ESR1-mutated disease, evERA’s HR of 0.38 was achieved against ET + everolimus—an active combination. Different populations, different comparators: cross-trial HRs cannot rank treatments. #BCSM @OncoAlert @OncoReporte @Larvol

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Fantastic discussion by super @BarbaraPistill2 at the oral abstract #BreastCancer session at #ESMO26 on ADCs in patients with HER2 low disease 👏👏👏👏 @OncoAlert @myESMO

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NICHE-2. Keeping it short because the plot speaks for itself. 1. Rename it Chalabi's disease 2. Stop operating on patients first For those who don't know: 111 patients with locally advanced dMMR colon cancer got one dose of ipi and two of nivo, then surgery. Zero events. A flat line. Next up? Avoid the surgery altogether. #ESMO2026 @Onco_Nexus @OncoAlert @TheGutOncLab

Fantastic summary slide of metastatic #bcsm #ADC landscape by @BarbaraPistill2 in her #ESMO26 discussion #ESMOAmbassadors @OncoAlert What do we need next??? 📍novel payloads 📍novel targets 📍data on sequencing

TALENT: neoadjuvant T-DXd, +/- anastrozole or TC, led to a disappointing pCR rate of <10% across arms for HR+ eBC. A hint of superior benefit was observed in patients with high HS-HER2 at baseline. Biomarkers clearly needed to unlock the potential of ADCs in the curative setting.

🇨🇳HORIZON-Breast06: Trastuzumab rezatecan widely outperformed chemo in endocrine-refractory HR+ MBC (PFS 16.6 vs 6.8 months, HR 0.25, p=0<0.01). Definitely passes the truck test. No significant OS, likely due to crossover of some patients to TOPO1 ADCs. #ESMO26 #ESMOAmbassadors

15-year results from NSABP B42. Extended AI after prior AI therapy led to a small yet significant advantage in 15y recurrence rate, mostly seen in node-positive disease (DRFS delta 4.4% N+, vs 1.6% N-). Important data to inform pts when deciding whether to extend ET. #ESMO26

Maintained iDFS benefit (Δ 5.3%) and favorable OS (Δ 2.1%) with adjuvant ribociclib after 6 years of follow up (all patients off ribo). Efficacy comparable to abema (monarchE), with different toxicity profile and wider population (N+ and high-risk N0). #ESMO26 #ESMOAmbassadors