Post by Professor Kefah Mokbel

NCCN Breast Cancer Guidelines v4.2026: What Actually Changed for Metastatic Disease The recurrent/stage IV section (JNCCN, July 2026) has several updates that meaningfully shift decision-making — not just recycled content. 𝗛𝗥+/𝗛𝗘𝗥𝟮+ 𝗺𝗮𝗶𝗻𝘁𝗲𝗻𝗮𝗻𝗰𝗲: PATINA is now published (NEJM 2026). Adding palbociclib to maintenance endocrine + anti-HER2 therapy extends median PFS from 29 to 44 months (HR 0.75) after induction chemo. Grade ≥3 AEs 81% vs 31% — real cost, real benefit. 𝗙𝗶𝗿𝘀𝘁-𝗹𝗶𝗻𝗲 𝗛𝗘𝗥𝟮+: DESTINY-Breast09 shows T-DXd + pertuzumab beating THP outright (PFS 40.7 vs 26.9 months, HR 0.46). NCCN still keeps THP preferred — lack of crossover in the trial (a stated guideline limitation) plus higher ILD/treatment-related mortality with T-DXd (12% ILD, 3.4% grade 5 vs 0.8%) likely underpin the cautious stance. 𝗧𝗡𝗕𝗖 𝗳𝗶𝗿𝘀𝘁 𝗹𝗶𝗻𝗲: ASCENT-04/KEYNOTE-D19 (NEJM 2026) — sacituzumab govitecan + pembrolizumab vs chemo + pembrolizumab in PD-L1+ disease: PFS 11.2 vs 7.8 months (HR 0.65). Now category 1 preferred, first ADC-IO combo in this setting. TROPION-Breast02 matures for PD-L1 CPS <10, no germline BRCA PV: datopotamab deruxtecan beats chemo on PFS (10.8 vs 5.6 months) and OS (23.7 vs 18.7 months) — now category 1 preferred in that population, on par with sacituzumab govitecan. 𝗘𝗦𝗥𝟭-𝗺𝘂𝘁𝗮𝘁𝗲𝗱 𝗱𝗶𝘀𝗲𝗮𝘀𝗲: VERITAC-2 adds vepdegestrant (PROTAC ER degrader) alongside elacestrant/imlunestrant — PFS 5.0 vs 2.1 months over fulvestrant (HR 0.58) in ESR1-mutant disease, though the trial missed its overall-population endpoint. 𝗢𝗦 𝗱𝗮𝘁𝗮 𝗻𝗼𝘄 𝗺𝗮𝘁𝘂𝗿𝗲 𝗳𝗼𝗿 𝘁𝘄𝗼 𝗣𝗜𝟯𝗞-𝗽𝗮𝘁𝗵𝘄𝗮𝘆 𝗿𝗲𝗴𝗶𝗺𝗲𝗻𝘀: INAVO120 shows fulvestrant/inavolisib/palbociclib with a 7-month OS advantage (34 vs 27 months, HR 0.67). CAPItello-291's updated analysis shows an estimated 18-month OS of 74% vs 65% with capivasertib/fulvestrant (HR 0.74) — median OS not yet reached in either arm. 𝗪𝗮𝘁𝗰𝗵 𝗯𝘂𝘁 𝗻𝗼𝘁 𝘆𝗲𝘁 𝗽𝗿𝗮𝗰𝘁𝗶𝗰𝗲-𝗰𝗵𝗮𝗻𝗴𝗶𝗻𝗴: AMBRE/PADMA (SABCS 2025 preliminary) suggest CDK4/6i + endocrine can match chemo even in high-visceral-burden HR+/HER2- disease — a direct challenge to reflexive chemo-first thinking. The guideline discusses these data in narrative text but hasn't incorporated them as a formal recommendation. The through-line: OS data finally catching up to PFS signals, and ADC-based combinations beginning to displace conventional chemotherapy backbones in selected first-line settings (notably PD-L1-positive TNBC). The THP-vs-T-DXd/pertuzumab question is the one to watch. https://lnkd.in/eGrDxnAP #BreastCancer #Oncology #NCCNGuidelines #OncoplasticSurgery #MetastaticBreastCancer #Oncodaily