🧵 Immune resistance in cancer. 🛡️ T-cell exclusion? Target macrophages with PI3Kγ inhibitors (e.g. IPI-549) to open the tumor to immune attack. Chronic interferon = double-edged sword. JAK inhibition redirects exhausted T cells back into action. PD-1 + LAG-3 = durable IO ⚡.

🚨 IO triplet in RCC hits turbulence. Zanzalintinib + nivolumab = 63% ORR, 18.5 mo PFS. ?benefit over Cabo/Nivo ?less HFS but similar activity. ➕ Adding relatlimab (triplet) ➡️ lower ORR & PFS.🔁 Rethink LAG3 as target RCC, it's not melanoma 😞. #ASCO25.

#SURE2: Sacituzumab + pembro: 44% CR and 71% bladder-intact EFS in MIBC patients refusing cystectomy.✂️ No chemo, no surgery.🔍 Biomarker-driven selection (luminal subtype, TMB) key?. Are we ready to skip cystectomy?.NMIBC recurrences an issue? .urineDNA to confirm CR?. #ASCO25.

5-yr data from KEYNOTE-564 confirms OS benefit for adjuvant #pembrolizumab in high-risk clear cell #RCC (HR 0.66). DFS & OS gains across subgroups. 🔥 Confirms OS benefit in adjuvant RCC.🧬 But are we overtreating 48% who never recur?.#ASCO25 #GUonc #Immunotherapy.

🚨 Practice-changing data at #ASCO25 in #CRC. 🔹 BREAKWATER: Encorafenib + cetuximab + FOLFOX doubles OS vs SOC (30.3 vs 15.1 mo) in BRAF V600E mCRC. 🔹 CheckMate 8HW: NIVO+IPI shows 54.1 mo PFS in MSI-H mCRC— new IO standard.

🚨 KRAS G12C in CRC: Combo strategies evolving fast. 🧪 G12C inhibitors + anti-EGFR (e.g. cetuximab) show synergy (ORR ~46%). 💥 Adding chemo may boost activity—but ⏫ toxicity, dose interruptions. 📌 Takeaways: – Drug exposure matters.– ctDNA ≠ always concordant. #ASCO25.

🧬 DYNAMIC-III shows ctDNA-guided chemo escalation in stage III colon cancer did not improve recurrence-free survival vs standard care. But ctDNA clearance post-chemo strongly predicts better outcomes. 40% pts persistent ctDNA despite chemo. Need new options #ASCO25 #CRC.

🧬 New hope for GU neuroendocrine carcinomas: DLL3-targeted T-cell engager shows a 40% response rate & ~8mo durability in DLL3-high tumors— outperforming chemo or IO in this poor-prognosis group. Biomarker-driven therapy may be here for small cell GU. #ASCO25 #OncTwitter #GUonc.

#ASCO25 Drug development session: Is HER3 the new HER2—or is it too soon? 🧬. HER3-targeting ADCs show promise in NSCLC & SCLC, but biomarker gaps, resistance issues and payload limits remain. “It’s not too early, but it’s not yet.” Lillian Siu.

What the #ASCO2025 AI session didn't cover fully (otherwise great talks).1️⃣ Genomic + multi-omic integration platforms.2️⃣ Health equity & bias audit needs.3️⃣ Clinician AI training urgent .4️⃣ Medico-legal liability frameworks for use.5️⃣ Environmental costs of large models ?🔌☢️.

Real-world AI in cancer care:.✅ ↑ in end-of-life discussions via AI nudges.✅ Increase nurse time in care (↓ documentation).✅ Faster trial screening & protein folding breakthroughs.But trust lags behind tech. Transparency, bias control & safety need urgent attention. #AIOnc.

🔍 AI in Oncology #ASCO2025.AI isn’t replacing oncologists—it’s augmenting care. Clinical decision support & ambient scribing to trial matching & drug discovery, AI improves efficiency, nudges evidence-based care, and supports overworked teams. Real challenge? Change management.

Vast majority of oncologists would counsel their own relatives and friends strongly to have chemotherapy if they had liver mets and CRPC progressing on ARPI. There's a role for patient choice, but a great responsibility on us to provide sound advice and weighting in fit pts.

Totally disagree with recruitment of patients with liver mets to CRPC trials that have a rotation to a different ARPI. There may be a role for that control arm in patients with PSA only or limited radiological progression. 1/2.

Enthusiastic audience response to #ASCO24 plenary abstracts today. Great that the organisers were able to schedule @TimmyTrumpet @tiesto @Alesso for after party

Fantastic to be back in Chicago catching up on data, catching up with friends @AlbigesL #ASCO24

RT @NicoGagelmann: Everytime after a conference🫢🤣

EV-Pembro is SOC for 1st line bladder cancer .50% of pts -> neuropathy . Note phase 1 of EV monoRx .1mg/kg cohort: neuropathy 19%, ORR 19% .1.25mg/kg cohort: neuropathy 38%, ORR 43% . Lesson: Don't dose reduce EV upfront.@DrRosenbergMSK @DanielPetrylak .

Did not have ‘Running through herd of goats’ on my #ESMO2023 bingo card. But I guess that’s the beauty of Casa de Campo and Madrid. Until next time!

Great collaboration with Australian centres. Pleasure to be involved in this. Congratulations @ChrisAleSei.